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H J Altermatt

Publications and source records attributed to H J Altermatt.

At least 55 records · Page 3Linked to original sources
PubMed1996

Coamplification in tumors of KRAS2, type 2 inositol 1,4,5 triphosphate receptor gene, and a novel human gene, KRAG.

Analysis of a region of DNA, coamplified in tumors with KRAS2, resulted in the identification of the human homologue of the mouse KRAG gene. The gene was widely expressed in a range of cell lines, tumors, and normal tissue and demonstrated a high degree of alternate splicing. A human KRAG cDNA sequence, with a structure similar to that encoded by the amplified gene in mouse Y1 adrenal carcinoma cells, was isolated by RT-PCR. The predicted amino acid similarity between the two sequences was 91%, and hydrophobicity plots suggested a structure closely resembling that of transmembrane 4 superfamily members. Identification of a PCR-based restriction fragment length polymorphism confirmed biallelic expression of KRAG but suggested allele-specific splicing differences in tumors. Northern analysis of mRNA derived from a range of tissues suggested high level expression in muscle and confirmed alternate splicing. To facilitate the analysis of exon junctions, a YAC clone encoding the genomic sequence was identified. This allowed the localization of KRAG to human chromosome 12p11.2. Isolation of one end of this nonchimeric clone demonstrated a perfect match with a 247-bp sequence within the 3' untranslated region of the type 2 1,4, 5-inositol triphosphate receptor gene. Multiplex PCR confirmed the inclusion of both genes in the KRAS2 amplicon in human malignancy, suggesting that either may contribute to the malignant phenotype.

Alleles↗
PubMed1996

Temperature and pressure effects during erbium laser stapedotomy.

BACKGROUND AND OBJECTIVES: Laser-assisted stapedotomy has become a well-established alternative to the mechanical drilling method. The goal of this study is to quantify the mechanical and thermal tissue effects and to determine optimum erbium laser parameters for safe clinical treatment. STUDY DESIGN/MATERIALS AND METHODS: On an inner ear model, time-resolved pressure measurements and Schlieren optical flash photography were performed during the perforation of the stapes foot plate using an erbium laser at 2.79 microns. The laser radiation was transmitted via an optical zirconium fluoride fiber. The laser-treated foot plates were investigated by light microscopy and scanning electron microscopy to visualise the laser-induced tissue effects. RESULTS: Perforation of the stapes foot plate can be performed with a few erbium laser pulses with high precision and a thermal damage zone of < 10 microns. Strong pressure transients were found to be generated by the bone ablation process and the collapse of a vapor channel created in the perilymph after fenestration. CONCLUSION: From the comparison of the laser-induced pressure with the limit graph to avoid hearing defects published by Pfander, an unobjectionable use of the erbium laser is deduced for fluences < 10 J/cm2. The erbium laser seems to represent an ideal instrument for middle ear surgery with all the advantages (precision, fiber optic transportable, high ablation efficiency, safety) desired for clinical application.

Erbium↗
PubMed1996

Intraoperative photodynamic therapy with m-tetrahydroxyphenylchlorin for chest malignancies.

BACKGROUND AND OBJECTIVE: Since there is no satisfactory treatment modality for diffuse malignant mesothelioma of the chest, we assessed surgical tumor resection followed by intraoperative photodynamic therapy with mTHPC in a phase I study. STUDY DESIGN/MATERIALS AND METHODS: Since 1990, eight patients have undergone intraoperative photodynamic therapy with m-tetrahydroxyphenylchlorin (mTHPC-PDT) following thoracotomy and surgical tumor resection. RESULTS: mTHPC-PDT-mediated tumor necrosis was characterized by tumor infarction due to tumor vessel necrosis and thrombosis, and its extent depended on drug-light conditions; 650 nm light delivered at 0.1 W/cm2 for 10 J/cm2 48 h after iv administration of 0.3 mg mTHPC/kg resulted in a 10-mm-deep complete tumor necrosis. Skin photosensitivity was related to the drug dose applied and occurred up to 17 days after iv administration of 0.3 mg mTHPC/kg, mTHPC-PDT of brachial plexus infiltrated by mesothelioma resulted in pain relief without deterioration of nerve function. CONCLUSION: Tumor resection and intraoperative mTHPC-PDT of the chest cavity is feasible under clinical conditions and offers local tumor control of sites involved. However, distant tumor spread was not prevented by this combined treatment modality and optimization of mTHPC-PDT is warranted for further intraoperative application.

Antineoplastic Agents↗
PubMed1996

Experimental and clinical results of fiberoptic argon laser stapedotomy.

Since 1992 a small air-cooled opthalmological argon laser (Argus system, 3 W max.) equipped with a fiberoptic microhandpiece has been used for stapedotomy at the Inselspital, Berne. The microhandpiece has been developed especially for otological purposes in our electronic laboratory. In order to measure the effect of argon laser pulses applied through the handpiece to the ear, we performed temperature measurements in a saline-filled inner ear model by using ultrathin (2 microns thick), ultrafast (4 ns) thermosensitive rhodamine-coated polyurethane films. Multiple laser pulses of 1-2.5 W and 0.1 s duration - as used in clinical applications - produced a temperature elevation of about 1 degree C in the liquid of the inner ear model. The local laser effect was then examined histologically on the isolated stapes. The thermal damage zone around the stapedotomy perforation was limited to about 100 microns. In a clinical study we compared the results of argon laser stapedotomy (n = 54) with those of a skeeter microdrill stapedotomy (n = 29). Substantial hearing gains were found in all cases in both groups. In the laser stapedotomy group the mean residual air-bone gap (0.5-2 kHz) was 10 dB or less in all cases but one. Inner ear function remained unchanged except for a 40-dB loss at 4000 Hz in one case. Transient vertigo with nystagmus occurred in one case. Facial nerve dysfunction did not occur in any patient. The most important advantage of the laser found was the absence of mechanical trauma to the stapes. Stapes luxation and a floating footplate were avoided. In contrast, thick footplates were more easily perforated with the skeeter. Use of an argon laser equipped with a fiberoptic microhandpiece and a skeeter microdrill as needed seems particularly advantageous for stapedotomy.

Equipment Design↗
PubMed1996

Experimental erbium laser surgery in the guinea pig cochlea: its use in the study of afferent cochlear neurotransmitters.

Microiontophoretic techniques were used to examine the changes in activity of inner half cell afferents in the guinea pig following circumscribed penetration of cochlear bone with erbium:YSGG laser pulses. Neuronal responses to the application of the glutamate agonists N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) before laser use and after return to normal spontaneous activity were equivalent, implying total reversibility of the changes occurring. Suppression of laser-induced hair cell activity was possible with NMDA and AMPA receptor antagonists and lasted 10-15 min. These findings suggest a transmitter-related increase of neuronal activity. Our results show that use of the erbium laser in inner ear microsurgery might be possible with low risk if the amount of energy applied is kept under a safe limit of 10 J/cm2.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1996

Video-assisted mediastinal lymph node dissection assessed in an experimental setting.

BACKGROUND: Feasibility, completeness, and morbidity of videoscopic-assisted mediastinal lymph node dissection (VATS MLND) were compared to the standard surgical technique in an experimental study. METHODS: Right upper MLND--together with upper lobectomy in half of the cases--was performed in ten large white pigs. Six animals were operated using VATS (group 1), four using conventional open techniques (group 2). After 1 week, the animals were sacrificed and the mediastinum was assessed for remaining lymph nodes. RESULTS: All animals survived without intra- or post-operative complications. There was no significant difference in the operation time between the two groups (3.2 +/- 0.8 vs 3.2 +/- 0.2 h). The number of mediastinal lymph nodes harvested was 9.5 +/- 2.7 in group 1 and 11.5 +/- 0.5 in group 2 (n.s.). The post-mortem assessment of the mediastinum showed in two animals of group 1 and in two animals of group 2 that one lymph node was left behind. In addition, in one animal of group 1 four small retrotracheal lymph nodes were found. CONCLUSIONS: VATS MLND can be accomplished without morbidity and is as radical as that achieved with conventional surgery in the paratracheal and peribronchial areas in this experimental setting. However, retrotracheal lymph node dissection might not be as complete as achieved by conventional surgery.

Animals↗
PubMed1996

Treatment of human papillomavirus-associated vulvar disease with the CO2-laser. Physical and histological aspects with use of a new scanning device, the SwiftLase.

The CO2-laser has a successful record in treatment of extensive, refractory vulvar condylomas and vulvar intraepithelial neoplasia. A prerequisite for optimal use of the laser is careful preoperative diagnosis and optimized surgical technique based upon the exact knowledge of the interaction process between laser radiation and tissue. Using a new CO2-laser scanning device, the Sharplan Swift-Lase, this in-vivo study analyses the effects of CO2-laser parameters [average power density (PD), beam size and exposure time] on vulvar skin to determine optimum laser settings. Our histomorphometric analyses reveal a minimal skin destruction (ablation depth 40 microns, extent of irreversible thermal damage 80 microns to 120 microns) after application of the CO2-laser energy with the SwiftLase using a PD of 1000 W/cm2 with a beam size of 1 mm diameter. Previous CO2-laser application techniques required low PD (200 W/cm2 to 750 W/cm2) and a larger beam size (1.5 mm to 2 mm) moving over the epithelial surface as fast as possible to obtain a precise skin destruction. The SwiftLase allows the laser beam to be moved slowly with a beam size of 1 mm and significantly higher PD (up to 5000 W/cm2). These advantageous application conditions guarantee precise, homogeneous vulvar skin treatments with minimal thermal damage to the surrounding normal skin. The SwiftLase enables a less experienced colposcopists to perform vulvar CO2-laser surgery.

Carcinoma in Situ↗
PubMed1996

Immunohistochemical characterization of subependymal giant cell astrocytomas.

Subependymal giant cell astrocytoma (SEGA) is the most common neoplastic process involving the brain in patients with tuberous sclerosis complex (TSC). Morphologically, these tumors exhibit a wide range of cytoarchitecture with spindle and epithelioid cells resembling astrocytes, and also large, occasionally giant cells, some of which have a distinctly ganglion-like appearance. Unresolved questions regarding SEGAs center on: (a) their cytogenesis, i.e., whether they are derived from single or multiple precursors; and (b) their differentiating capacity along glial or neuronal lines. We sought to determine whether SEGAs represent truly mixed tumors or whether they consist of a single population of cells with a capacity for divergent differentiation. Twenty SEGAs were assessed for immunophenotypic features of either neuronal or glial differentiation or both. Only tumors from patients with a clinically confirmed diagnosis of TSC were included. Immunoreactivity for glial fibrillary acidic protein (GFAP) and/or S-100 protein was considered indicative of a glial phenotype, whereas the presence of neuronal differentiation was assessed by staining for cytoskeletal proteins [neurofilament epitopes, class III Beta-tubulin, microtubule-associated protein 2 (MAP2), synaptophysin], neurosecretory substances [serotonin, cholecystokinin, Beta-endorphin, substance P, somatostatin, metenkephalin, neuropeptide Y, vasoactive intestinal polypeptide (VIP), and for the 28-kDa neuron-associated calcium binding protein calbindin. Of the tumors examined, 18 exhibited both glial and neuronal epitopes, the staining pattern being variable. In 19 tumors, the constituent spindle, polygonal and giant or ganglion-like cells showed variable immunoreactivity for GFAP and S-100 proteins both within the cell body and processes. Neuron-associated cytoskeletal proteins were present in 18 cases. Class III Beta-tubulin immunoreactivity was demonstrated in 17 tumors, both within the bodies of all three cell types and to varying degrees within their processes. Neurofilament protein and calbindin staining was present in 8 tumors, with reactivity for the former being distributed in a phosphorylation-dependent manner. MAP2 was detected in a few cells of two tumors. Immunoreactivity for neuropeptides was observed in 17 lesions. Somatostatin and metenkephalin staining was noted in 10 tumors (50%) being present particularly within polygonal cells. Neuropeptide Y, serotonin and Beta-endorphin reactivity was found in 6 (30%), 5 (25%), and 4 tumors (20%), respectively; Beta-endorphin was lacking in giant cells, whereas neuropeptide Y and serotonin were seen within their cell bodies. Substance P and VIP were evident in only occasional polygonal cells of 2 (10%) and 1 tumor (5%), respectively. Stains for cholecystokinin were negative. The observation of immunoreactivity for both glial- and neuron-associated epitopes within tumor cells of the same morphology suggests that SEGAs represent proliferations of cell lineages with the capacity to undergo divergent glioneuronal as well as neuroendocrine differentiation to a greater extent than do other mixed glial-neuronal neoplasms.

Adolescent↗
PubMed1996

High levels of loss at the 17p telomere suggest the close proximity of a tumour suppressor.

High levels of loss of distal markers on 17p13.3 in breast cancer suggested the presence within the region of at least one tumour-suppressor gene. Here we describe the derivation of two biallelic polymorphisms from the 17p telomeric yeast artificial chromosome (YAC) TYAC98. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and multiplex PCR analysis demonstrated that the high level of allelic imbalance observed in breast tumours represented loss of constitutional heterozygosity (LOH) and that this LOH extended to the telomere. Lung carcinoma (but not Wilms' tumour)-derived DNA again revealed a high level of loss of subtelomeric 17p sequences. Telomeric microsatellite polymorphisms from other chromosome arms did not show such elevated loss in either tumour type. This suggested that the 17p loss observed did not reflect a general telomeric instability and provided further evidence for the presence of a breast cancer tumour-suppressor gene in the distal region of 17p13.3.

Breast Neoplasms↗
PubMed1996

Prognostic significance of CCND1 (cyclin D1) overexpression in primary resected non-small-cell lung cancer.

Amplification of the CCDN1 gene encoding cyclin D1 was examined by Southern blotting and multiplex polymerase chain reaction (PCR) and occurred in 8 of 53 patients (15%) with primary resected non-small-cell lung cancer (NSCLC). These tumours and 17 additional tumours with a normal gene copy number showed overexpression of cyclin D1 (25/53, 47%), as assessed by immunostaining using a monoclonal antibody. In 22/25 cases, cyclin D1 was localised in the cytoplasm, but some (7/25) had simultaneous nuclear staining. This result is in marked contrast to that reported in breast, hepatocellular and colorectal carcinoma studies where immunostaining was invariably nuclear. Examination of a restriction fragment length polymorphic (RFLP) site within the 3'untranslated region of the cDNA following reverse transcriptase (RT)-PCR (29/53 informative cases) showed a strong association between cytoplasmic staining and imbalance in allele-specific message levels. Cyclin D1 overexpression was associated with a poorly differentiated histology (P = 0.04), less lymphocytic infiltration of the tumour (P = 0.02) and a reduction in local relapse rate (P = 0.01). The relative risk of local relapse was 9.1 in tumours without cyclin D1 overexpression (P = 0.01, Cox regression analysis). We conclude that genetic alteration of cyclin D1 is a key abnormality in lung carcinogenesis and may have diagnostic and prognostic importance in the treatment of resectable NSCLC.

Aged↗
PubMed1996

[Pathogenesis of otosclerosis. "State of the art"].

Women suffer from otosclerosis 1.6 times more often than males. Histologically, otosclerotic foci can be found in temporal bones of females 1.9 times more often than in those of males. Characteristic topographic regions are the oval window, round window niche and promontory. Otosclerosis can also occur principally in any area of the enchondral/periosteal layer of the otic capsule. Evidence is presented that otosclerosis is an inflammatory tissue reaction associated with macrophages, T- and B-lymphocytes, HLA-DR positive cells and plasma cells. Dependent on the stage of the osteolytic bone disease present deposits of complement and immunoglobulins (IgG, IgA) can be found. These immunoglobulins have been identified as antibodies to measles virus proteins. Using the polymerase chain reaction we were successful in demonstrating RNA sequences of measles viruses in otosclerotic bone from footplates removed during stapes surgery. Since most of the otosclerotic lesions were in direct contact to the perilymphatic space, it may be expected that the endolymphatic sac--as the immune competent organ of the inner ear--specifically reacts to antigens delivered from the otosclerosis focus into the perilymph. Perilymph samples from patients were collected during stapes surgery and their antibody titers against measles were compared with that in corresponding blood serum. All samples revealed a significantly elevated-specific anti-measles IgG amount which was significantly higher than in the corresponding serum. In contrast, antibody titer in the perilymph against herpes simplex or cytomegalo viruses did not differ from that of the serum. These findings indicate that otosclerosis is a measles virus associated inflammatory osteolytic disease of the temporal bone. Since women suffer from severe measles virus infections more often than males, it can be hypothesized that females have a higher susceptibility of their cochleo-vestibular tissues to these infections (organotropism). In addition, estrogens are well-known stimulators of osteocytic activity and may play a dominant role during ossification of an otospongeotic bone lesion. This may explain the onset of a conductive hearing loss due to otosclerosis during pregnancy.

Adult↗
PubMed1995

Paradoxical effects of bleomycin and heavy water (D2O) in mice.

Bleomycin (BLM) lacks many side effects of other cytostatic drugs. Pulmonary toxicity is the major dose-limiting effect of BLM. This is based in part on generation of free radicals. It is conceivable that deuterium in body fluids lessens the production of free radicals, thus preventing or diminishing the morphologic expression of pulmonary BLM toxicity. We therefore studied the effect of moderate deuteration of body fluids on BLM-induced lung damage in BALB/c-mice. In addition to conventional histopathological methods, we used a vertical sectioning design for stereological estimation of pulmonary volumes and surface areas. BLM (low/medium/high dose: 25/50/75 IU/kg body weight) was injected i.p. once a week for 6 weeks. Half the mice drank deuterated water before, during and after BLM treatment. Three weeks after the last injection, the lungs were fixed by airway instillation. Deuterated animals treated with BLM lacked signs of irreversible BLM-induced pulmonary damage. Conversely, focal sub-pleural fibrosis and fibrosing alveolitis were present in BLM-treated mice drinking tap water. Deuterated mice had stereological values for almost all lung parameters that were lower than in non-deuterated mice. The organ-specific advantage of deuteration was offset by marked enhancement of systemic toxicity of BLM. We conclude that (1) moderate concentrations of deuterium may prevent the development of fibrosing alveolitis in BLM-treated mice, possibly by reducing proliferation of alveolar fibroblasts, and, less probably, by impairing generation or enhancing capture of free radicals; (2) the toxicity of BLM was enhanced by ingestion of deuterium, resulting in morphological liver alterations and increased mortality.

Animals↗
PubMed1995

Alternate splicing produces a novel cyclin D1 transcript.

Using Northern blotting and PCR analysis of cDNA derived from a range of cell lines and tissues, alternate splicing of the cyclin D1 gene (CCND1) mRNA has been demonstrated. The variant transcript shows no splicing at the downstream exon 4 boundary, encoding a protein with an altered carboxy-terminal domain. Investigation of mRNA extracted from mononuclear cells, lung tumour and normal tissue suggests that both transcripts are invariably expressed. However, splicing to produce the two forms of mRNA is modulated, in the heterozygote, by a frequent A/G polymorphism located within the splice donor region of exon 4. Preliminary analysis of patients with resectable non-small cell lung cancer suggests that genotype is associated with shortened event free survival and greater risk of local relapse.

Aged↗
PubMed1995

Olfactory neuroblastoma. An immunohistochemical, ultrastructural, and flow cytometric study.

BACKGROUND: Olfactory neuroblastoma is an uncommon neuroectodermal tumor of the upper nasal cavity, microscopic features of which are not always homogeneous. No morphologic features have been found to correlate reliably with prognosis. METHODS: Twenty-six olfactory neuroblastomas occurring in 14 females and 12 males, ages 18-78 years, were studied by immunohistochemistry, electron microscopy, and DNA flow cytometry. Survival rates were statistically analyzed relative to several variables. RESULTS: Microscopically, 22 tumors formed a morphologic spectrum intermediate between paraganglioma (PG) and neuroblastoma (NB). Others included two ganglioneuroblastomas (GNB), one lesion exhibited biphasic (neuronal and epithelial) differentiation, and one tumor showed predominantly epithelial features. Immunoreactivity for neuronal and neuroendocrine markers included synaptophysin in 77%, neurofilament protein in 38%, class III beta-tubulin in 81%, and chromogranin A in 77%. In 88% of cases, elongated S-100 protein-positive cells surrounded tumor lobules. Cytokeratin and epithelial membrane antigen immunoreactivity were noted in six (23%) and two (8%) tumors, respectively. Aberrant p53 expression was detected in 16 tumors (62%). The Ki-67 labeling index (LI) varied from 0%-43.8% (mean, 7.4%). Ultrastructurally, 80-230 nm dense core granules were noted within perikarya and as in microtubule-containing processes in all of the 11 tumors studied by electromicroscopy. Lobules of seven tumors were surrounded by electron-dense sustentacular cells. Epithelial tumors exhibited obviously epithelial features in addition to neuronal differentiation. DNA flow cytometry demonstrated a high incidence of polyploidy and aneuploidy (78%) and a wide range of percent S phase fractions (1.5%-21.8%; mean, 9.0%). The study showed that longer survival rates are related significantly to (1) the occurrence of metastases which was linked to tumor subtype, (2) to a higher incidence of S-100 protein-positive cells, and (3) to a low (< 10%) Ki-67 labeling index. CONCLUSIONS: The present study indicates that (1) although typical olfactory neuroblastomas exhibit PG/NB differentiation, they more closely resemble PG, (2) occasional tumors show GNB and/or epithelial differentiation, and (3) survival rates may correlate with S-100 protein immunoreactivity and Ki-67 LI. Cancer 1995; 76:4-19.

Adult↗
PubMed1995

Plastic hollow waveguides: properties and possibilities as a flexible radiation delivery system for CO2-laser radiation.

BACKGROUND AND OBJECTIVES: One significant inconvenience of the CO2 laser is the lack of flexible fibers essential for endoscopic applications. The goal of this study is to test the feasibility of hollow waveguides in view of a practical use in medicine. STUDY DESIGN/MATERIALS AND METHODS: Various types of plastic hollow waveguides for flexible delivery of CO2 laser radiation were examined. The transmission losses, divergence angle, damage threshold, and input and output beam profiles were determined. The interaction process between radiation transmitted through these guides with soft as well as hard tissues was studied. RESULTS: Plastic hollow waveguides can transmit high power (up to 50 W) with low losses (straight guide 1 dB/m) even through bendings. The divergence angle is < 13 degrees. Cutting quality and extent of thermal damage are comparable to incisions performed with a free laser beam. CONCLUSION: The results of this study show good cutting quality and durability of these flexible plastic hollow waveguides, which render possible to deliver CO2 radiation in the power range needed for most surgical applications with affordable transmission losses. Plastic hollow waveguides are, therefore, a real alternative to replace the mirror arms.

Animals↗
PubMed1995

Tuber and subependymal giant cell astrocytoma associated with tuberous sclerosis: an immunohistochemical, ultrastructural, and immunoelectron and microscopic study.

The cellular nature of the giant eosinophilic cells of tuber and of the cells comprising subependymal giant cell astrocytoma (SEGA) in tuberous sclerosis (TS) remains unclear. To assess the characteristics of these lesions, 13 tubers and 6 SEGA were immunohistochemically studied with glial and neuron-associated antigens. In addition to conventional ultrastructure, 6 tubers and 8 SEGA were subjected to immunoelectron microscopic study for glial fibrillary acidic protein (GFAP) and somatostatin. Eosinophilic giant cells of tubers were positive for vimentin (100%), GFAP (77%) and S-100 protein (92%); such cells were also found to a various extent to be reactive for neuron-associated antigens, including neurofilament (NF) proteins (38%) or class III beta-tubulin (77%). SEGA also showed variable immunoreactivity for GFAP (50%) or for S-100 protein (100%); NF epitopes, class III beta-tubulin, and calbindin 28-kD were expressed in 2 (33%), 5 (83%) and 4 (67%) cases, respectively. Cytoplasmic staining for somatostatin (50%), met-enkephalin (50%), 5-hydroxytryptamine (33%), beta-endorphin (33%) and neuropeptide Y (17%) was noted in SEGA, but not in tubers. Ultrastructurally, the giant cells of tubers and the cells of SEGA contained numerous intermediate filaments, frequent lysosomes and occasional rectangular or rhomboid membrane-bound crystalloids exhibiting lamellar periodicity and structural transition to lysosomes. Some SEGA cells showed features suggestive of neuronal differentiation, including stacks of rough endoplasmic reticulum, occasional microtubules and a few dense-core granules. Furthermore, in one case of tuber, a process of a single large cell was seen to be engaged in synapse formation. Intermediate filaments within a few cells of both lesions were decorated by gold particle-labeled GFAP antiserum. Within the tumor cells of SEGA, irregular, non-membrane-bound, electron-lucent areas often contained somatostatin-immunoreactive particles, whereas the latter could not be detected in tuber. The present study provides further evidence of divergent glioneuronal differentiation, both in the giant cells of tubers and the cells of SEGA. The findings of similar cells at different sites, including the subependymal zone, white matter ("heterotopias"), and cortex indirectly supports the idea that these lesions of TS result from a migration abnormality.

Adolescent↗
PubMed1995

Glucocorticoid and progesterone inhibit involution and programmed cell death in the mouse mammary gland.

Milk production during lactation is a consequence of the suckling stimulus and the presence of glucocorticoids, prolactin, and insulin. After weaning the glucocorticoid hormone level drops, secretory mammary epithelial cells die by programmed cell death and the gland is prepared for a new pregnancy. We studied the role of steroid hormones and prolactin on the mammary gland structure, milk protein synthesis, and on programmed cell death. Slow-release plastic pellets containing individual hormones were implanted into a single mammary gland at lactation. At the same time the pups were removed and the consequences of the release of hormones were investigated histologically and biochemically. We found a local inhibition of involution in the vicinity of deoxycorticosterone- and progesterone-release pellets while prolactin-release pellets were ineffective. Dexamethasone, a very stable and potent glucocorticoid hormone analogue, inhibited involution and programmed cell death in all the mammary glands. It led to an accumulation of milk in the glands and was accompanied by an induction of protein kinase A, AP-1 DNA binding activity and elevated c-fos, junB, and junD mRNA levels. Several potential target genes of AP-1 such as stromelysin-1, c-jun, and SGP-2 that are induced during normal involution were strongly inhibited in dexamethasone-treated animals. Our results suggest that the cross-talk between steroid hormone receptors and AP-1 previously described in cells in culture leads to an impairment of AP-1 activity and to an inhibition of involution in the mammary gland implying that programmed cell death in the postlactational mammary gland depends on functional AP-1.

Animals↗