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Biomedical subjects

J B Hansen

Publications and source records attributed to J B Hansen.

At least 109 records · Page 6Linked to original sources

[A group of homosexuals change their sex habits after information about AIDS. A questionnaire survey].

A questionnaire investigation to which 144 homosexual persons replied anonomously revealed alterations in the sexual habits after information about AIDS. Significant reduction in the annual number of partners and significantly fewer employ the more dangerous sexual practices which now occur particularly in more permanent partnerships are among the alterations started. An unchanged number still employ active anal and orogenital coitus. Employment of condoms has increased significantly, particularly in anal coitus and "casual" partners (from 3% to 82%). The majority accept the use of condoms and state that they employ more "safe sex" than prior to information about AIDS. 12% stated that they had sex with both sexes and the possibility of spread of infection from homosexual to heterosexual groups is present. The intensive informative work from the homosexuals own organisation and from public health authorities appear to have had some effect but further information and influencing are necessary if the spread of HIV infection is to be stopped.

Acquired Immunodeficiency Syndrome↗

The effect of lipopolysaccharides (LPS) on generation of thromboxane A2 and thromboplastin activity in whole blood of males, females and females on oral contraceptives.

Heparinized blood sample taken from 81 healthy persons, 40 men and 41 women of whom 17 were on combined oral contraceptives, were incubated with 2 ng lipopolysaccharides (LPS)/ml blood. Quantitation of thromboxane B2 (TxB2) in the resultant plasma revealed a significantly (p less than 0.001) higher generation of TxB2 in men than in women. No sexual differences were observed in thromboplastin activity in unstimulated and LPS stimulated monocytes. Addition of liposomes together with LPS enhanced the synthesis of thromboplastin 2-10 fold and unveiled a higher synthesis of thromboplastin among men. No differences were observed in TxB2 and thromboplastin synthesis in blood collected from females or females using oral contraceptives. A significant correlation between TxB2 and the thromboplastin activity exists within the male (r = 0.46, p = 0.003) and the oral contraceptive (r = 0.57, p = 0.016) group after exposure to LPS. This study suggests that males exposed to LPS may generate more thromboxane A2 than females and thus be at higher risk of developing thrombosis.

Adult↗

Effects of dietary supplementation with cod liver oil on monocyte thromboplastin synthesis, coagulation and fibrinolysis.

In a controlled trial 40 healthy persons (20 men and 20 women) were tested before and after a daily supplement with 25 ml cod liver oil for 8 weeks. The diet increased the eicosapentaenoic acid (20:5 n-3) content in serum and monocytes four- to five-fold whereas the arachidonic acid (20:4 n-6) content decreased 10-20% in both serum and monocytes. Stimulation of blood with a low concentration of lipopolysaccharides (LPS) revealed a 40% suppression of LPS-induced thromboplastin synthesis in the monocytes after 8 weeks of CLO intake. In the same LPS stimulation system, men were found to generate significantly more thromboxane B2 than women (4.9 ng ml-1 versus 3.4 ng ml-1). After the CLO supplementation for 8 weeks the thromboxane B2 was reduced by a mean of 70% in women and 60% in men. Factor VII and fibrinogen appeared to be unaltered by CLO intake. Determination of whole blood clot lysis time and tissue plasminogen activator (t-PA) did not indicate any significant influence of n-3 fatty acids on fibrinolysis.

Adult↗

Centrifugation of very freshly donated blood may yield platelets unstable to storage in the new generation of containers.

The stability of platelets stored in the second generation of container has been examined further. Platelet concentrates prepared in CPD anticoagulant were found to deteriorate fairly rapidly during storage if prepared from very freshly donated blood, whereas a more than 4-hour delay between donation and platelet isolation yielded platelet concentrates much more stable to storage. Delays of more than 2 h (relative to the time of donation) in the isolation of platelets led to decreases in the aggregation response to low or moderate doses of collagen. Platelets from blood collected into CPD adenine showed decreased aggregation responses relative to equivalent cells from blood collected into adenine-free anticoagulant. It seems that a decreased aggregation response is associated with improved storage properties.

Adenine↗

LHRH analogue as a depot preparation (Zoladex) in the treatment of advanced carcinoma of the prostate followed by orchiectomy as a second line therapy--a phase II study.

An LHRH agonist, Zoladex, was employed as a monthly depot in 56 previously untreated patients with advanced carcinoma of the prostate. Of 53 evaluable patients, 27 achieved partial remission and 7 were stable. Median duration of response was 10 months. A favorable subjective response was attained in 68% of the patients. During treatment, serum testosterone was in the castrate range in all patients except five. Possible explanations for this escape phenomenon are discussed. No toxicity was observed and treatment was well tolerated in all patients. Thirty-two patients underwent bilateral orchiectomy following treatment failure of Zoladex. In one patient partial remission according to protocol criteria was recorded. Treatment with LHRH agonists seems safe and may serve as an alternative to conventional hormonal treatment of advanced carcinoma of the prostate.

Aged↗

Fatty acids, platelets and monocytes. Something to do with atherogenesis.

A remarkable variation in monocyte activation among individuals was observed when blood from different people was incubated with lipopolysaccharides. To elucidate this phenomenon, we studied intracellular signals associated with monocyte activation. This was done by measuring induced thromboplastin synthesis. An inhibitor of phospholipase A2 blocked the lipopolysaccharide induced synthesis of thromboplastin. Thus, release of arachidonic acid (20: 4) seemed to be necessary to activate the monocytes. Nordihydroguaiaretic acid, a lipoxygenase inhibitor, had no effect on the monocyte activation in subjects with a low response to lipopolysaccharides (low responders); this contrasted with nearly 80% inhibition in individuals with very sensitive cells (high responders). Taking aspirin raised monocyte activation by an average of 50%, this was caused by the effect of aspirin on the platelets. Platelets enhanced the lipopolysaccharide activation of monocytes 2-3 fold. The high response phenomenon was partially due to platelets. When platelets in the blood of high responders were substituted with platelets from low responders, the monocyte activation fell by up to 70%. Fatty acids seemed to play a central role in the activation of monocytes. Intake of cod liver resulted in significant reduction of induced thromboplastin synthesis. It is suggested that those who are high responders may be more susceptible to developing atherosclerosis.

Arteriosclerosis↗

Psoralenamines. 3. Synthesis, pharmacological behavior, and DNA binding of 5-(aminomethyl)-8-methoxy-, 5-[[(3-aminopropyl)oxy]methyl]-, and 8-[(3-aminopropyl)oxy]psoralen derivatives.

A series of derivatives of 5-(aminomethyl)-8-methoxypsoralens, 8-[(3-aminopropyl)oxy]psoralens, and 5-[[[3-(tri-methylammonio)propyl]methyl]-8-methoxypsoralen has been synthesized and their potential as PUVA reagents examined. While the DNA association constants of selected psoralens were found to be 10(5)-10(6)L mol-1, corresponding to efficient binding, flow linear dichroism studies indicated that only the 8-substituted psoralens bind to DNA by intercalation. Furthermore, the ability to photoinduce interstrand cross-links in calf thymus DNA, in vitro, was as efficient as that of 8-methoxypsoralen for the 8-substituted psoralens, which were up to 25 times as efficient as the 5-substituted psoralens. Four of the psoralens studied were radiolabeled and used to study photobinding to DNA. Analogously to the cross-binding results, the 8-substituted psoralens were more efficiently photobound than the 5-substituted, while only slight differences were found in the photobinding-cross-linking ratio. The photoreactivity of the aminopsoralens toward cyclohexene and 2'-deoxythymidine was enhanced compared to that of 8-methoxypsoralen, the effect being most pronounced when the amino group is close to the furocoumarin ring system. Most of the new compounds were less photocytotoxic than 8-methoxypsoralen to NHIK 3025 cells, in vitro, and they caused less light-induced DNA interstrand cross-linking, in situ, in these cells. A clear correlation between the photocytotoxicity and the DNA cross-linking ability of the psoralens was observed. Several of the derivatives showed more pronounced effects in the light-dependent skin thickening (inflammatory) test on mice than 8-methoxypsoralen. No correlation between DNA cross-linking capacity, in vitro, and skin phototoxicity was found for this series of psoralens.

Animals↗

Distribution of Alginate Lyase Activity among Strains of Bacillus circulans.

Strains from four different DNA relatedness groups of Bacillus circulans showed apparent alginate lyase activity; the activity of three strains examined had mannuronidase specificity. A representative strain of group 4 also produced apparent inducible unsulfated chrondroitin lyase activity.

Journal Article↗

Distinct bacteriocin groups correlate with different groups of Streptococcus mutans plasmids.

A correlation between the presence of 5.6-kilobase plasmids and bacteriocin activity was found in human-derived strains of Streptococcus mutans. Compared with bacteriocin activity of randomly selected clinical isolates of plasmid-negative strains, bacteriocin activity of plasmid-positive strains significantly inhibited not only two laboratory strains of S. mutans, OMZ176 and AHT (P less than 0.0001 and P = 0.038, respectively), but most plasmid-negative clinical isolates as well (P = 0.0005). Comparisons of inhibition between pairs of plasmid-positive strains revealed two groups, group I and group II, that produced distinct bacteriocins we designated as mutacin I and mutacin II, respectively. Within each group, a strain produced inhibitory activity against all the members of the other group but against no members of its own group. Plasmid DNA from plasmid-positive strains of each group was isolated and analyzed by restriction endonuclease digestion. Plasmids from the two groups that were apparently identical in size differed in digestion patterns for EcoRI, HaeIII, and TaqI, even though six TaqI fragments appeared to be common to all. Based on bacteriocin profiles and restriction enzyme digests, two distinct groups of plasmid-positive S. mutans strains emerged. Although the bacteriocin activity of plasmid-positive strain LM7 (serotype e) placed it in group I, clear differences in restriction digests distinguished it from the other plasmid-containing strains.

Bacteriocins↗

Photochemical cross-linking of protein and DNA in chromatin. Synthesis and application of a photosensitive cleavable derivative of 9-aminoacridine with two photoprobes connected through a disulphide-containing linker.

A novel cleavable photo-cross-linking reagent, N-(2-methoxy-6-azidoacridin-9-yl)-N'-(4-azidobenzoyl)cystamine, for analysis of protein-nucleic acid interactions, has been synthesized. The reagent contains two photosensitive groups that can be activated sequentially. The azidoacridinyl moiety is sensitive to u.v. and visible light (lambda less than or equal to 450 nm), whereas the azidobenzoyl part needs higher-energy light (lambda less than or equal to 350 nm). Furthermore, the disulphide bridge connecting the two photoactive groups can be cleaved by reduction with mercaptans. The reagent is shown to induce cleavable cross-links between all five major histones and DNA in chromatin from Ehrlich ascites cells on activation with long-wavelength u.v. light (lambda greater than 300 nm) at an efficiency of approximately 3% of the added reagent.

Azides↗

Alginase enzyme production by Bacillus circulans.

Stream and soil samples were screened for microorganisms that would use alginate from mucoid Pseudomonas aeruginosa as the sole carbon and energy source. A pure culture containing large aerobic rods was isolated. The cells were about 0.8 by 2.5 microns in size, had lateral or peritrichous flagella, had a negative Gram stain reaction, and produced spores on sporulation medium. Purified DNA was approximately 46 mol% G+C as measured by thermal denaturation. From these and other biochemical tests, the organism was identified as Bacillus circulans. The enzyme activity that degraded alginate appeared in the culture medium. Upon gel filtration, alginase activity eluted as a single peak at a position corresponding to a protein of 40,000 daltons. Activity recovered from this one-step, partial purification showed apparent endomannuronidase specificity. Like other alginases previously reported, the enzyme appeared likely to be a lyase (or eliminase). However, no Bacillus species or other gram-positive bacteria have heretofore been reported to produce extracellular enzymes with alginase activity. Several other B. circulans strains from the American Type Culture Collection also appeared to have inducible extracellular alginase activity.

Alginates↗

Acridine-psoralen amines and their interaction with deoxyribonucleic acid.

A series of novel compounds in which a 9-acridinyl nucleus is linked to a psoralen nucleus in the 5- or 8-position via polyamines was prepared and examined. Their reversible binding to DNA and their irreversible binding to DNA and DNA cross-linking upon irradiation with UV-A light were examined. It was found that they were all less efficiently photoreactive than 8-methoxypsoralen (8-MOP), both in cross-linking and photobinding to DNA, whereas the ratio between their photobinding and cross-linking was 40-400 times that of 8-MOP. Compounds in which the linker was attached to the 5-position in psoralen showed smaller cross-linking and photobinding efficiencies and larger ratios between photobinding and cross-linking than those of psoralens attached in the 8-position. This strongly indicates that the 9-substituents of the acridines are oriented toward the minor groove. Flow linear dichroism studies showed that the compounds were DNA intercalating with the acridine moiety, whereas the psoralen moiety in no case was clearly intercalating. This conclusion was further supported by viscometry which also strongly indicated monointercalation.

Acridines↗

Determination of the dissociation constant of a weak acid using a dissolution rate method.

Based on theories of diffusion-controlled mass transport for dissolution processes of weak acids in aqueous alkaline media, a method for the determination of the dissociation constant of a weak monoprotic acid is described. The method includes measurements of the initial dissolution rate as a function of pH, using the rotating-disk technique, and determination of the intrinsic solubility. The method was applied to determine the apparent dissociation constant (mu = 0.1) of 5,5-dimethyl-3-(alpha,alpha,alpha,4-tetrafluoro-m-tolyl)hydantoin, a new schistosomicide. For comparison, a spectrophotometric method for the pKa determination was developed. Due to rapid hydrolysis of the compound in the pH range required for the determination of the pKa, the development of the latter method turned out to be complicated and tedious. The results of both methods were in good agreement. For compounds with unfavorable properties for titrimetric or spectrophotometric determination of the pKa value, the dissolution rate method can be a useful alternative.

Hydrogen-Ion Concentration↗