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Biomedical subjects

S Sommer

Publications and source records attributed to S Sommer.

At least 127 records · Page 7Linked to original sources

Photodynamic therapy of C3H mouse mammary carcinoma with haematoporphyrin di-ethers as sensitizers.

Haematoporphyrin di-ethers were synthesized and tested as sensitizers for photodynamic therapy of C3H/Tif mammary tumours in mice. Growth curves of the tumours were determined by measuring the tumour volume. The animals were given 25 mg porphyrins kg-1 body weight i.p. and 24 h later exposed to 135 J cm-2 of 630 nm light at a fluence rate of 150 mW cm-2. The sensitizing efficiency of the ethers was measured in terms of the increase in growth time of the treated tumours, as compared with that of untreated controls, needed to reach a volume 5 times larger than that at the time of the treatment. This sensitizing efficiency increased with decreasing polarity, i.e. in the order di-methyl ether, di-propyl ether, dibutyl ether and di-amyl ether. Haematoporphyrin di-amyl ether was more efficient than haematoporphyrin derivative and insignificantly less efficient than photofrin II (DHE). This was true for sensitization of both tumours and normal tissue.

Animals↗

Intake of marine fat, rich in (n-3)-polyunsaturated fatty acids, may increase birthweight by prolonging gestation.

Birthweights in the Faroe Islands are among the highest in the world. Compared with Denmark, the average birthweight of liveborn singleton infants of primiparous mothers is 194 g higher, and a substantial part of this difference seems to be attributable to longer gestation. Prostaglandins play an important part in the timing of parturition in human beings. Dietary (n-3)-polyunsaturated fatty acids (PUFA) in high amounts influence endogenous prostaglandin metabolism. Owing to the large consumption of marine fat, the average intake of (n-3)-PUFA in the Faroes by far exceeds that in Denmark. The hypothesis proposed is that dietary (n-3)-PUFA in high amounts prolong gestation in human beings by interfering with uterine production of prostaglandins, possibly by inhibiting the production of dienoic prostaglandins, primarily PGF2 alpha and PGE2, which are mediators of uterine contractions and cervical ripening.

Animals↗

SOS induction by thermosensitive replication mutants of miniF plasmid.

MiniF, a 9.3 kb fragment of the dispensable F plasmid, carries genes necessary for its replication and partition as well as for the expression of an SOS signal. The arrest of replication of a thermo-sensitive miniFts at 42 degrees C induced SOS functions such as prophage lambda, sfiA expression, W-reactivation of UV-irradiated phage lambda. Two miniF ts9 and ts17 mutations were located within the KpnI fragment (43.6-46.9) in the minimal oriS replicon. Blocking miniF replication by incBC+ incompatibility genes situated in trans on a second plasmid also induced SOS functions. In contrast, if miniFts17 plasmid escaped the replication block at 42 degrees C by being inserted into pR325, there was no SOS induction. SOS induction by the arrest of miniF replication required the miniF lynA+ locus in cis, the host recA+ and lexA+ genes. We found that SOS induction was increased greatly near the stationary phase and that cell viability declined. During host cell exponential growth, miniFts9 and miniFts17 plasmids were lost rapidly, although SOS induction persisted for several cell generations. We postulate that lynA expresses a persistent product that may lead to the unwinding of chromosomal DNA.

Bacterial Proteins↗

Urological complications after total hip replacement.

Two cases of acute (partial) obstruction of the ureter following total hip replacement ad modum Charnley are reported. The two cases are found to be caused by action from an intrapelvic cement plug. Similar cases from the literature are referred.

Aged↗

Mini-F plasmid-induced SOS signal in Escherichia coli is RecBC dependent.

Dispensable replicons such as F plasmid [95 kilobases (kb)] or its mini-derivatives such as mini-F (9.3 kb) or lambda mini-F efficiently induced cellular SOS genes such as sfiA (sulA) when they were damaged by UV irradiation and then introduced into a recipient bacterium. To generate an SOS signal, UV light-damaged mini-F or mini-F conditional mutants deficient in replication required that the bacterial RecBC enzyme retained some activity different from the nuclease activity that was dispensable. In contrast, UV light-damaged F plasmid produced an SOS signal independently of the activity of the RecBC enzyme and of the expression of the mini-F, -H, and -G proteins. Our findings are consistent with a picture in which the SOS signal is constituted by stretches of single-stranded DNA on a replicon. Moreover, our present data combined with other data previously published lead to the hypothesis that the SOS signal induced by mini-F plasmid is located in trans on the host chromosome, whereas the one generated by UV light-damaged F plasmid is in cis on the transferred DNA.

Chromosomes, Bacterial↗

Oxygen dependence of the photosensitizing effect of hematoporphyrin derivative in NHIK 3025 cells.

Cells of the established line NHIK 3025 were incubated with hematoporphyrin derivative and exposed to light at different concentrations of oxygen. The efficiency of photoinactivation of the sensitized cells decreased with decreasing oxygen concentration. No photoinactivation was observed when the atmosphere above the medium overlying the cells was pure N2 gas. With 1% O2 in the atmosphere, the quantum yield of photoinactivation was reduced by 50% compared to the yield in air-saturated medium. It is hardly possible to inactivate cells in anoxic regions of a tumor by means of porphyrin sensitized photochemotherapy. In spite of this, the therapy seems to be efficient in several cases. Thus, it seems that anoxic tumor cells are inactivated in secondary reactions, probably due to breakdown of the circulatory system in the tumor.

Carcinoma in Situ↗

Formation of metal complexes of tumor-localizing porphyrins.

Whereas the tumor localizer and photosensitizer hematoporphyrin derivative (Hpd) has its fluorescence emission maximum at 610-630 nm, several authors have reported that in aqueous solutions of hematoporphyrin (Hp) and Hpd, or in tumors after an injection of Hpd, a compound is formed which has its fluorescence emission maximum at 570-590 nm. This work (HPLC and fluorescence analysis) indicates that this peak is due to the formation of Zn-porphyrins either in vitro or in vivo. Cu- and Co-porphyrins may be formed as well, from traces of these metallic ions. In contrast to free porphyrins and Zn-porphyrins the latter complexes are non-fluorescent and do not act as photosensitizers.

Animals↗

Tumor-localizing and photosensitizing properties of the main components of hematoporphyrin derivative.

Both 3H-labeled and unlabeled hematoporphyrin derivative (HPD) were analyzed by high-pressure liquid chromatography (HPLC) and gel permeation chromatography. Four main components were isolated by HPLC, and two were isolated by gel permeation chromatography. The tumor-localizing ability of each component was tested and compared to that of 67Ga and 3H2O by injection in mice bearing Lewis lung carcinoma. The photosensitizing abilities of the HPLC-separated components in vitro were also tested. Finally, porphyrin extracts of tumors from mice given HPD were analyzed by HPLC. The tumor-localizing ability of the components increased with decreasing polarity. While crude HPD localized in tumor tissue only to the same extent as did 3H2O, Component 7 was almost as effective as was 67Ga in localizing in the tumor. The cellular uptake of HPD components increased with decreasing polarity. In accordance with this, the low-polarity components were the most effective photosensitizers.

Animals↗

Uptake of the components of hematoporphyrin derivative by cells and tumours.

The porphyrin content of cells labelled with hematoporhyrin derivative (Hpd) and tumours of mice injected with Hpd was analysed by means of high pressure liquid chromatography (HPLC). The components of Hpd may be classified in 3 groups: (A) Components with a high fluorescence quantum yield and with sharp peaks in the HPLC chromatogram. These are monomers. (B) Components with a lower fluorescence quantum yield and with sharp peaks in the HPLC chromatogram. These are probably dimers or oligomers. (C) Components with a low fluorescence quantum yield, with a short retention time on a P-10 column and with a broad and unresolved peak in the HPLC chromatogram. These are probably large aggregates. Components of group A are rapidly accumulated by cells but are easily removed by washing the cells with medium containing serum. Porphyrins of group B are significantly more concentrated by cells in vitro than porphyrins of group A and B and accumulate over a time interval of about 18 h. Porphyrins of group B gradually migrate to sites in the cells where they are more strongly retained. Tumors in mice behave differently from tumor cells in vitro since they mainly contain porphyrins of group C after an i.p. injection of Hpd in the mice.

Animals↗

The main photosensitizing components of hematoporphyrin derivative.

Commercial hematoporphyrin (Hp) and the tumor-localizing and photosensitizing agent hematoporphyrin derivative (Hpd) were analysed by means of high pressure lipid chromatography (HPLC). Furthermore, their efficiencies in sensitizing the photoinactivation of human cells in vitro were compared. The comparison showed that the least polar components of Hpd played the major role in this sensitization. In Hpd solutions used for injection in photochemotherapeutic treatment of cancer, these active components seem to be present as aggregates.

Cell Line↗

Human papillomavirus. Frequency and distribution in plantar and common warts.

Fifty-nine (24 plantar, 35 common) warts surgically excised from 44 patients (15 female, 29 male), 18 to 32 years old, were examined by electron microscopy (EM) for papillomavirus particles and by fluorescent antibody (FA) and peroxidase-antiperoxidase (PAP) tests for human papillomavirus type 1 (HPV-1)-specific antigens and papillomavirus genus-specific (common) antigens. Fifty per cent of plantar warts and 52 per cent of common warts were positive for HPV by EM. When examined by FA and PAP for genus-specific antigens, 58 per cent of plantar warts and 68 per cent of common warts were positive. Fifty per cent of plantar warts and 11 per cent of common warts were caused by HPV-1 as determined by reactivity with HPV-1 type-specific antiserum. All warts positive by EM were positive by FA and PAP. Sampling error accounted for warts positive by FA and PAP but not by EM. Forty-two per cent of plantar warts and 31 per cent of common warts were negative by both EM and FA and PAP. The warts caused by HPV-1 contained more virus and were more clinically aggressive than warts caused by other HPV. This study shows that the results obtained by the PAP technique using papillomavirus genus- and type-specific antisera on formalin-fixed, paraffin-embedded tissue available to the diagnostic pathologist are concordant with the results obtained by methodology usually available only to the experimental pathologist.

Adolescent↗