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Biomedical subjects

H J Altermatt

Publications and source records attributed to H J Altermatt.

At least 73 records · Page 4Linked to original sources

The significance of the human endolymphatic sac and its possible role in Menière's disease.

Modern immunohistochemical methods allow a functional characterization of the human endolymphatic sac (ES) and its associated cell populations. The currently available immunohistochemical data of the extraosseous part of the human ES support the assumption that the epithelium is metabolically active and capable of both secretion and adsorption. The reactivity of the epithelial cells with antibodies against neuroendocrine antigens imply a paracrine activity of the human ES. Further results provide evidence for a possible role of the human ES in inner ear immune defence and indicate a putative functional relationship of the human ES to the common mucosa-associated immune system (MALT).

Cell Division↗

Expression and activity of cell cycle regulators during proliferation and programmed cell death in the mammary gland.

In the mammary gland distinct phases of proliferation, differentiation and programmed cell death of epithelial cells occur at defined stages of development. Here we show that the expression and activity of cell cycle regulators during normal and preneoplastic proliferation and programmed cell death are remarkably similar. In all cases we found elevated levels of a protein kinase A activity and of transcription factor AP-1, cFos and JunD being the major components of the AP-1 DNA binding complex. A correlation between cFos and JunD expression and chromosomal DNA fragmentation during programmed cell death was observed. Several genes associated with G1, including cyclin D1, D2 and D3 and c-fos, c-jun, junB, JunD, c-myc and p53, are induced in proliferating and in apoptotic mouse mammary tissue. Whereas the expression of these genes correlated with active proliferation of epithelial cells in terminal end buds during puberty, very little proliferation or DNA synthesis, but, instead, extensive apoptosis of epithelial cells, was observed during involution. Our results suggest that a G1-like state is associated with programmed cell death of mammary epithelial cells in vivo and that apoptosis occurs without S-phase induction.

Journal Article↗

Production of endometrial placental protein 14 and prolactin by cultured endometrial explants after collagenase and freeze/thaw treatment, and in response to progesterone.

OBJECTIVE: Investigation of methods for maintaining functional endometrial explants in culture after cryopreservation with or without previous enzymatic dispersion of stromal cells and epithelial glands. Such a standardized culture system is a requirement for the development of a non-invasive bioassay for embryo quality in in vitro fertilization programs, a method that will eventually measure endometrial response to embryo conditioned media. METHOD: Culture of mid-luteal phase endometrial biopsies, in the presence of [35S]methionine, with or without prior collagenase treatment and/or storage in liquid nitrogen in the presence of dimethyl sulfoxide. Determination of released de novo synthesized total protein by trichloroacetic acid precipitation of culture media. Measurement, after culture in absence and presence of progesterone, of prolactin and placental protein 14 (PP14) production by sensitive non-isotopic immunoassays. RESULTS: Production of prolactin, but not PP14, was increased by 200 nmol/l progesterone, 2-8-fold after 4 days and 1.5-700-fold after 7 days in culture. After limited collagenase treatment (but without separation of stromal cells from glands), both marker protein productions were similar compared to untreated explants; however, there was no significant stimulation of prolactin by progesterone. After freezing and thawing, production was markedly reduced, particularly from explants frozen following collagenase treatment. CONCLUSIONS: Both stromal and glandular viability are maintained after collagenase treatment but the response to progesterone is lost. Cryopreservation reduced prolactin and PP14 production in subsequent culture. Therefore, novel freezing protocols should be developed which preserve both endometrial structure and function.

Collagenases↗

Parallel assessment of glutathione-based detoxifying enzymes, O6-alkylguanine-DNA alkyltransferase and P-glycoprotein as indicators of drug resistance in tumor and normal lung of patients with lung cancer.

The levels of several potential indicators of drug resistance were measured in tumor and corresponding normal tissue of 55 untreated patients with lung cancer. The resistance parameters include glutathione (GSH) level, activities of the enzymes glutathione transferase (GST), glutathione peroxidase (GPx) and O6-alkylguanine-DNA alkyltransferase (ATase), as well as expression of P-glycoprotein (Pgp). Median values of GSH, GST and GPx were significantly higher in tumor than in normal tissue of non-small-cell lung cancer (NSCLC) or of small-cell lung cancer (SCLC), whereas ATase was elevated in tumor tissue of NSCLC only. Pgp expression as determined by Western blotting was significantly lower in tumor than in normal tissue of NSCLC. Resistance-parameter expression did not correlate with stage of disease or age of the patients. We found a negative correlation between smoking intensity and GSH level in normal tissue. Our findings indicate that the fundamental differences in chemosensitivity between SCLC and NSCLC cannot be explained by differences in the GSH-system or in the expression of Pgp. However, the level of ATase activity may be one of the factors responsible for the difference in chemosensitivity.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Expression of stromelysin-1 and TIMP-1 in the involuting mammary gland and in early invasive tumors of the mouse.

The mammary gland, during post-lactational involution, is subjected to extensive tissue reconstruction. This process is governed by the concerted expression of extracellular-matrix-degrading enzymes and their inhibitors. During carcinogenesis, the invasive growth of tumor cells is characterized by the penetration of the basement membrane and stromal invasion. We compared the expression of the tissue-remodeling enzymes stromelysin-1, a matrix metalloproteinase, and its inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1), during mammary gland involution and carcinogenesis in mouse. In involuting mammary glands, stromelysin-1 was expressed in myoepithelial cells, whereas TIMP-1 was confined to the stromal tissue. To analyze the involvement of these tissue-remodeling genes in tumor development, we examined mammary tumors of transgenic mice expressing either the activated Ha-ras or c-myc oncogene under the control of a milk-protein gene promoter. In the undifferentiated and metastasizing Ha-ras-induced tumors, stromelysin-1 expression was comparable to that seen in involution, whereas TIMP-1 expression was greatly elevated. During Ha-ras-induced carcinogenesis, stromelysin-1 expression was first detected in the myo-epithelial cells surrounding preneoplastic lesions. In contrast, in the well-differentiated and non-metastatic mammary tumors induced by c-myc, no expression of either gene was observed. Thus, expression of stromelysin-1 and TIMP-1 is confined to the aggressively growing tumors and is induced in the earliest stages of carcinogenesis.

Animals↗

[Autoimmune processes as paraneoplastic manifestations in familial breast carcinoma].

In two patients, mother and daughter, with breast cancer a paraneoplastic syndrome of probably autoimmune pathogenesis developed in the course of the neoplastic disease. In the mother the cancer occurred when she was aged 51, first in the left and then, 4 years later, in the right breast. A local recurrence 18 years later caused a pericardial effusion and further tumour recurrences were associated with symptoms like those in Sjögren's syndrome, as well as bullous pemphigoid and polyneuropathy. Antinuclear antibodies, extractable nuclear antigen antibodies and rheuma factors were demonstrated in serum. Both symptoms and antibody titres regressed under treatment with tamoxifen and various cytostatic drugs. The patient died aged 74 years.--The daughter underwent a lumpectomy for breast cancer when aged 39 years, followed by mastectomy for local recurrence after 2 years. A further 2 years later she was found to be anaemic with a positive Coombs test (1:1024) and antibodies against IgG and complement. Metastases developed later. In her case, too, clinical and serological findings clearly regressed under treatment with tamoxifen and chemotherapy. She died, aged 45 years, from the consequences of further metastases.

Adult↗

Effects of various laser types and beam transmission methods on female organ tissue in the pig: an in vitro study.

The purpose of this in vitro study was to investigate and compare effects of various laser types (CO2, Argon, Erbium:YAG, Erbium:YSGG, and Holmium:YAG) and laser beam transmission methods (optical lens and flexible fiber) on ovarian and uterine tissue of the pig. The Erbium laser radiation was transmitted through Zirconium fluoride fibers (ZrF4). To circumvent the low mechanical stability of these fibers, we developed a special microlens system, which refocuses the radiation and protects the distal end from damage. Tissue lesions were performed with 1 and 5 joule. Histologic analysis of acute Er:YAG laser lesions reveal precise cutting effects with a minimal thermal damage zone of 40 microns and a high damage resistance of the fiber microlens systems. The extent of thermal damage caused by the Erbium:YSGG and CO2 laser is about two times larger, whereas the Argon and Holmium laser tissue lesions show a damage of the surrounding tissue of 200-300 microns. This study suggests that for precise cutting and coagulation, Erbium and Holmium lasers transmitted via our modified fiber tip may render the use of these lasers possible in a wide range of laparoscopic surgery applications.

Animals↗

Permeation of human chorioamniotic membranes by Escherichia coli in vitro.

OBJECTIVE: Our goal was to study the permeation of Escherichia coli through human chorioamniotic membranes in vitro. STUDY DESIGN: Medium was placed in two compartments separated by chorioamniotic membranes obtained from six cesarean sections at term. The compartment faced by the chorion was inoculated with E. coli. Both compartments were sampled over 12 hours for observation of bacterial growth. Controls were performed without membranes. RESULTS: In the compartment that was inoculated, concentration of E. coli increased from 10(6) to 10(10) colony-forming units per milliliter. In the compartment faced by amnion, bacterial growth was observed after 6 hours and reached 10(3) colony-forming units per milliliter. Permeation of E. coli was confirmed histopathologically. The change of glucose and lactate was linear. In the controls the concentration of E. coli increased to 10(7) (p < 0.001). CONCLUSIONS: E. coli organisms permeate viable chorioamniotic membranes. The membranes constitute a weak barrier against ascending infection and do not inhibit bacterial growth.

Amnion↗

[Urogenital malformation complex including the Mullerian system].

Symptomatic cystic epididymis in a 21-year-old man led to the detection of several genital malformations, including a partially obstructing pelvic cyst, prostatic and bilateral testicular atrophy and penoscrotal hypospadias. These malformations are probably due to a deficiency of either testosterone or müllerian inhibiting hormone (MIH). Development of the male genitalia is influenced by testosterone secreted in the Leydig cells during weeks 8-16 of gestation, while regression of the müllerian ducts is induced by MIH secreted in the Sertoli cells from weeks 9-12 of gestation.

Abnormalities, Multiple↗

Photodynamic therapy with m-tetrahydroxyphenylchlorin in vivo: optimization of the therapeutic index.

The therapeutic index of meta-tetrahydroxyphenylchlorin-mediated photodynamic therapy (mTHPC-PDT) was assessed in BALB/c nude mice bearing human malignant mesothelioma xenografts. Equal doses of 650 nm laser light were delivered to the tumour and to an equal-sized area of the hind leg (control site) after i.p. administration of mTHPC. Twenty-one groups of 6 animals each were treated under various drug-light conditions and at drug-light intervals ranging from 4 hr to 6 days. After light delivery the extent of tumour necrosis and the depth of alterations in normal tissue were assessed by light microscopy of standardized histological sections. A therapeutic index (TI) of mTHPC-PDT was defined as the cross-sectional area of tumour necrosis per depth of visible tissue injury at the control site. This TI was strongly related to the conditions of treatment. In particular, it was increased by prolonging the drug-light interval up to 5 days and by increasing the dose of light for any dose of drug. The most profound increase of TI was obtained by increasing the intensity of light administered at the chosen interval while reducing the dose of drug. Our findings suggest that threshold conditions operate in PDT and have important implications for clinical application of the treatment.

Animals↗

Effect of drug-light interval on photodynamic therapy with meta-tetrahydroxyphenylchlorin in malignant mesothelioma.

The influence of the time interval (TI) between drug administration and laser activation on selectivity of meta-tetrahydroxyphenylchlorin(mTHPC)-mediated photodynamic therapy (PDT) for tumour tissue was assessed in BALB/c nude mice bearing human malignant mesothelioma xenografts. Following i.p. administration of 0.3 mg/kg mTHPC, a light dose of 10 J/cm2 and 0.1 W/cm2 was delivered at 650 nm on the tumour and an equal-sized area of the hind leg after 4, 12, 24 and 36 hr and 2, 3, 4, 5 and 6 days to groups of 6 animals (surface irradiance). Then, 72 hr after light delivery, the depth of necrosis was measured in the tumour and in the skin and underlying muscle of the hind leg. Photosensitized necrosis occurred in normal tissue at TI from 4 hr to 3 days and in the tumour at TI from 12 hr to 4 days. The therapeutic ratio of mTHPC-PDT varied significantly with the time interval between drug administration and laser activation and was greatest at an interval of 3 days. mTHPC concentration was measured in 3 control unirradiated animals at all time points in normal tissues and in tumour tissue, and found to be the same in both tissues. Thus the tissue concentration of mTHPC was of limited use as regards the prediction of photosensitizing effects in the tumour model.

Animals↗

Absence of rhodamine 123-photochemotoxicity in human tumor xenografts.

Rhodamine 123 (R123)-photochemotoxicity was assessed in BALB/c nude mice bearing a xenografted human squamous cell carcinoma at various power densities and wavelengths and a given incident fluence of 150 Joules/cm2. One hour before light delivery, 1 mg R123/kg was injected i.p. in 20 animals. Surface irradiance was performed on the tumor and an equal size hind leg area of 40 animals. Three groups of 10 animals were treated at 514.5 nm and 0.1 W/cm2, 1 W/cm2, and 30 W/cm2, and one at 488 nm and 30 W/cm2. In each group, five animals received R123. The R123 concentration was measured in the tumor (0.023 +/- 0.007 micrograms/g) and tumor-free tissue (0.023 +/- 0.008 micrograms/g) in three additional animals by high performance liquid chromatography 1 hour after R123-administration. Histologic assessment 72 hours after light delivery revealed no tissue damage at nonthermal power densities, either in the tumor or in the tumor-free tissue, irrespective of R123-administration. At 30 W/cm2, neither in the tumor nor in tumor-free tissues was there any significant difference in the depth of necrosis, irrespective of R123-administration and the wavelength applied. Our results question the validity of R123 as a photosensitizer, at least in this rodent tumor model.

Animals↗

Lasers in endoscopic surgery.

Lasers provide the endoscopic surgeon with a sophisticated tool for high precision cutting, destruction of tissue and coagulation. The laser allows efficient and time-saving operating techniques. Various laser systems emitting at different wavelengths are available. The absorption of the laser is determined by the tissue properties, such as water content or pigmentation, and varies strongly with the wavelength. Each laser offers advantages for the treatment of specific disorders. Further data from clinical studies are required to evaluate whether the advantages found in experimental studies are of significance in clinical use.

Female↗