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Biomedical subjects

S Kirchner

Publications and source records attributed to S Kirchner.

35 records · Page 2Linked to original sources

Cell cycle disturbance in relation to micronucleus formation induced by the carcinogenic estrogen diethylstilbestrol.

In addition to its tumor-promoting activity in hormone-receptive tissue, the carcinogenic estrogen diethylstilbestrol (DES) has been found to induce cell transformation, aneuploidy and micronucleus formation in mammalian cells. The majority of these micronuclei contained whole chromosomes and were formed during mitosis. Here a possible relationship between a disturbance in cell cycle progression and micronucleus formation is investigated by exposing Syrian hamster embryo (SHE) cells to DES. Continuous bromodeoxyuridine labeling followed by bivariate Hoechst 33258/ethidium bromide flow cytometry was employed for analysis of cell cycle transit and related to the time course of micronucleus formation. Treatment of SHE cells with DES resulted in delayed and impaired cell activation (exit from the G0/G1 phase), impaired S-phase transit and, mainly, G2-phase traverse. Cells forming micronuclei, on the other hand, were predominantly in G2 phase during DES treatment. These results suggest that impairment of S and G2 transit may involve a process ultimately leading to micronucleus formation.

Animals↗

Cytogenetic changes in primary, immortalized and malignant mammalian cells.

Some chromosomes in transformed rat cells and somatic cell hybrids fail to display the presence of kinetochore proteins as detected by antikinetochore antibodies. Such chromosomes (K- chromosomes) may constitute a novel mechanism for the genesis of aneuploidy. We have analyzed primary, immortalized and malignant mammalian cells for the presence of kinetochore proteins and micronuclei. Our results suggest a correlation of the K- chromosome and micronucleus frequency with the variability in chromosome number. Upon in situ hybridization with the minor satellite and alpha satellite sequences some K- chromosomes showed a signal. This indicates that the observed lack of kinetochores is not necessarily due to a lack of centromeric DNA. We conclude that dislocated K- chromosomes may become incorporated into micronuclei which are prone to loss. Such events would be associated with the generation of aneuploidy.

3T3 Cells↗

An investigation of micronucleus and mutation induction by oxazepam in mammalian cells.

The benzodiazepines are a class of drugs that are widely used in the treatment of various psychiatric disorders. One member of this class, oxazepam, is also a common metabolite of several other benzodiazepines. Since the evidence for the genetic toxicity and carcinogenic properties of these compounds is inconsistent, we investigated the oxazepam-induced formation of micronuclei in Syrian Hamster embryo fibroblast (SHE) cells, human amniotic fluid fibroblast-like (AFFL) cells and L5178Y mouse cells. A dose-dependent increase in micronucleus fractions was found in all three cell lines. The time course of micronucleus induction in L5178Y cells showed a maximum at 5 h after treatment, suggesting that the micronuclei were formed in the first mitosis after treatment. Kinetochore staining (CREST-antiserum) revealed the presence of kinetochores in approximately 50% of the micronuclei in all three cell types. This result was further confirmed by in situ hybridization in L5178Y cells and indicates the presence of whole chromosomes or centric fragments as well as acentric fragments in the oxazepam-induced micronuclei. The L5178Y cells did not show a mutagenic response to oxazepam at any of the doses or expression times used.

Animals↗

The mechanism of the solute-induced chain interdigitation in phosphatidylcholine vesicles and characterization of the isothermal phase transitions by means of dynamic light scattering.

A new method is introduced for the detection of chain interdigitation in phospholipid bilayers. The same method is used to measure the hydrocarbon tilt in the dipalmitoylphosphatidylcholine membranes as a function of the bulk concentration of the interdigitation-inducing solutes, such as ethanol. The hydrocarbon tilt in the phosphatidylcholine bilayers is demonstrated to be limited to angles below approx. 51 degrees. The need for higher tilt values leads to bilayer interdigitation. Solute-induced chain interdigitation is shown to be a cooperative process provoked by the excessively large lateral repulsion in the interfacial region and the concomitant excessive chain tilt. Ethanol-induced phosphatidylcholine interdigitation, for example, proceeds via interdigitated domains formation and finally gives rise to the bilayers with fully intercalated chains tilted by at least 30 degrees (and sometimes as much as 50 degrees) with respect to the membrane normal.

Ethanol↗

Removal of the antibacterial activity of trimethoprim-sulfamethoxazole, ofloxacin and zidovudine by BACTEC resin-containing blood culture medium.

We determined the capacity of BACTEC resin blood culture media NR 16A and NR 17A to remove the antibacterial activity of trimethoprim-sulfamethoxazole, ofloxacin and zidovudine. Simulated blood cultures containing increasing antibiotic concentrations were inoculated with 10(1), 10(3) and 10(5) CFU/ml blood of various bacterial strains and evaluated with the BACTEC infrared growth detection system. The antibiotic concentrations were adjusted to give breakpoint concentration in the added serum volume or in the total volume of the blood culture vials. Recovery rates and time until detection of bacterial growth in resin-media were compared with those in resin-free media. Trimethoprim-sulfamethoxazole and ofloxacin were, similar to piperacillin, inactivated by resins at antibiotic concentrations that were up to ten times higher than those easily achievable in serum. The antimicrobial effect of zidovudine on gram negative bacteria was reduced in resin media at concentrations corresponding to fifteen times the peak serum levels. Growth of P. aeruginosa, but not of S. aureus, E. coli, K. pneumoniae and Salmonella, was delayed in the presence of resins even at subinhibitory antibiotic concentrations when compared with resin-free media.

Bacteremia↗

Resin versus standard blood culture media used with the new BACTEC automated infrared system: an evaluation in febrile granulocytopenic patients.

Resin-containing aerobic and anaerobic blood culture media (NR 16A and NR 17A) for use with the new BACTEC infrared blood cultures system were compared with standard BACTEC media (NR 6A and NR 7A) in their efficacy to detect bacteremia in febrile granulocytopenic patients receiving antimicrobial treatment. A total of 1185 sets of blood cultures obtained from 341 patients during a 12-month period were evaluated. There were 109 positive cultures (9.2%) with 128 pathogenic organisms isolated from 52 patients (15.2%). Statistically significant differences were found between aerobic media, but not between anaerobic media. Aerobic resin bottles (NR 16A) were more often positive (90 versus 78, p less than 0.05) than standard aerobic bottles (NR 6A). They yielded a higher number of microorganismS (98 versus 80, p less than 0.05) per culture and per culture-positive patient (53 versus 42, p less than 0.01). NR 16A cultures also were more often positive after 1-day incubation (44% versus 21%, p less than 0.01) than NR 6A cultures and allowed earlier subcultivation. The use of NR 16A medium instead of resin-free aerobic NR 6A medium may enhance the detection of bacteremia in selected groups of patients receiving antimicrobial treatment, and can shorten the time until detection of bacteremia.

Agranulocytosis↗

Histology of sun-damaged human skin.

In glycomethacrylate sections of sun-exposed skin, we found the epidermis a sensitive index of damage. The stratum corneum of severely damaged skin was often compact and laminated, or gelatinous, and sometimes contained vesicles full of proteinous material. These vesicles arose from the enlarged and distinctly cellular-thick stratum lucidum. Sometimes there was no clear transition between the stratum lucidum and corneum. In the malpighian layer, cell heterogeneity, vacuolization, dysplasia, and zonal necrosis were common. The number of Langerhans cells was reduced in sun-damaged epidermis. The dermis had the usual disparate degrees of elastotic changes, with the formation of amorphous masses and the occurrence of fiber breakdown (fibrorhexis and fibrolysis). Macrophages among the elastotic masses contained coarse granules. When stained by means of the hematoxylin and Lee technique, the elastotic masses in the papillary dermis were pink or red but those in the mid dermis stained lilac to blue; all other elastic fibers stained pink or red. We found reticulin fibers predominantly around the elastotic masses and in areas of fibrorhexis and/or fibrolysis; a delicate collagenous fiber scaffolding supported the elastotic masses.

Adult↗

[Corticoid allergy].

A 50-year-old female patient developed maculopapular exanthema after administration of corticoids on account of a cervical syndrome. Under topical therapy with different corticoids because of an allergic contact eczema, the skin lesions worsened and consecutive oral corticoid therapy again induced maculopapular exanthema. Skin tests revealed an eczematous contact allergy to the stereoisomeric corticoids dexamethasone and beta-methasone, as well as to two salts of these substances. Furthermore, allergies to other ingredients of the vehicles were detected. The various allergic clinical manifestations, the allergologically important corticoids, the test procedures and sensitization conditions are discussed in correlation with the literature.

Administration, Topical↗

Native healing in Alaska. Report from Serpentine Hot Springs.

Traditional Alaskan Native healing practices, specifically sweat bathing and hot springs bathing, have medical connotations in that they involve sociocultural factors important to practicing medicine among Alaskan Native people. At Serpentine Hot Springs in northwest Alaska, relief for arthritis, back pain, hip pain, headaches, skin rashes and other disorders was sought. The "treatment setting" was an informal bathhouse and bunkhouse and Eskimo tribal doctors and patients were assigned tasks related to healing. Continuity with traditional cultural patterns was achieved in several ways: meals tended to be traditional Eskimo fare, the predominant language spoken was Inupiaq and styles of interaction were Inupiat in character. All patients showed improvement. The experience reported herein is instructive for those seeking innovative approaches treating Native American groups.

Adult↗

[Multiple granulomata pyogenica in a patient with acne vulgaris (author's transl)].

Multiple granulomata pyogenica are usually satellites of a primary lesion recently treated unsuccessfully. Disseminated pyogenic granulomas are very uncommon. In our case report, we describe a young man with six granulomata pyogenica over the chest, after treating his acne with tetracycline and vitamin A acid. In the discussion, we include infection, trauma and vitamin A acid as factors which can induce the vascular tumor in the region of a vascular dysplasia.

Acne Vulgaris↗

Hepatic hemangioendothelioma. Angiographic appearance and apparent prednisone responsiveness.

A 6-month-old girl was seen because of multiple cutaneous hemangiomas, hepatomegaly, and failure to thrive. A liver scan with technetium Tc 99m sulfur colloid showed two filling defects in the left lobe. Diffuse nodular hepatic lesions characteristic of hemangioendotheliomas were disclosed by celiac angiography and confirmed by biopsy. Congestive heart failure, present in many infants with this syndrome, was not manifest. Prednisone was administered, 2 mg/kg, on alternate days. Liver size and cutaneous hamangiomas promptly regressed in size and "catch up" linear growth occurred during six months of treatment. Congestive heart failure did not develop. Sixteen months after treatment, liver size and a second hepatic scan were normal.

Celiac Artery↗