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F Bittinger

Publications and source records attributed to F Bittinger.

At least 19 recordsLinked to original sources
PubMed2003

[Endosonographically controlled transluminal fine needle aspiration biopsy: diagnostic quality by cytologic and histopathologic classification].

BACKGROUND AND OBJECTIVE: EUS-guided fine needle aspiration (EUS-FNA) has emerged as a highly accurate technique for detecting and classifying mediastinal and pancreatic lesions as well as abdominal and recently retroperitoneal masses with a minimum of risk for the patient. PATIENTS AND METHODS: To objectify these statements, we evaluated the quality of 72 EUS-FNA specimens by cytologic and histopathologic classification, investigated their contamination with tissue from the needle pathway and observed puncture-related complications in a retrospective study of 44 EUS-FNA in 41 consecutive patients (56 +/- 14 years, m = 24, f = 17; 13 pancreatic, 9 adrenal, 6 abdominal and 13 mediastinal masses). EUS-FNA was performed using a PENTAX 32 UA endosonoscope (longitudinal 7.5 MHz sector array) in combination with a needle system type "Hancke-Vilmann". RESULTS: 16 vs. 11 of 34 histopathologic and 38 cytologic specimens were classified "excellent", 7 vs. 10 "sufficient", 7 vs. 13 "poor" and 4 vs. 4 "failed". Analysis of contamination with tissue from the needle pathway showed 4 vs. 2 specimens "highly", 3 vs. 14 "clearly", 8 vs. 19 "slightly" and 19 vs. 3 "not" contaminated. Specimens classified "excellent" were less contaminated (p = 0,037). EUS-FNA identified 35 benign and 24 malignant masses. Definite diagnosis failed in 13 specimens. One nonfatal complication occurred. EUS-FNA is an accurate (89 %) and low-risk procedure to examine primary undiagnosed mediastinal, pancreatic, intraabdominal and especially adrenal lesions in most of the cases. Contamination with tissue from the needle pathway seems to be a major predictive factor of poor specimen quality and failed diagnosis. CONCLUSION: EUS-FNA expands the diagnostic approach of mediastinal, abdominal, pancreatic and adrenal masses and provides accurate specimens for reaching new differential-diagnostic competence, especially in endocrinologic cases.

Abdominal Neoplasms↗
PubMed2003

Chromosomal aberrations in premalignant and malignant squamous epithelium.

Biopsies of oropharyngeal cancer were screened for chromosomal imbalances by comparative genomic hybridization (CGH) performed on 22 primary tumors and morphologically nonmalignant surrounding mucosa. The aim was to determine early chromosomal changes of tumor development and to draw conclusions on the mechanisms leading to multiple tumors. The most prominent chromosomal imbalances observed were over representations of genomic material on 3q, 15q, 8q, and 11q and losses on 9p, 3p, and 11q. In morphologically normal mucosa collected at 1 cm from the primary tumor border (M1), amplifications on 15q and 21q were most frequent. Far fewer gains and losses were found in M1 than in the primary tumor (average 2.2 vs. 6.9). Gains dominated over losses, but a tendency toward an increasing proportion of losses in the primary tumor (PT) was observed (ratio of gains to losses: PT, 4.75; M1, 6.3). Almost all the imbalances in M1 were detected in the primary tumor. No chromosomal alterations were identified with CGH in tissue samples dissected at 2 cm from the primary tumor (M2). In all samples, dysplastic morphologic changes decreased with distance from the primary tumor, which correlates with the observed lower level of genetic changes. We suggest that gains of genetic material on 15q and 21q are early events in malignant progression of squamous cell carcinoma, followed by gains on 3q, 8q, and 11q, and losses on 3p and 9p at later stages. Based on our cytogenetic data, we discuss the monoclonal model followed by lateral epithelial spread as an explanation of multiple head and neck squamous cell carcinomas.

Adult↗
PubMed2002

Tissue response and biomaterial integration: the efficacy of in vitro methods.

Implantation involves tissue trauma, which evokes an inflammatory response, coupled to a wound healing reaction, involving angiogenesis, fibroblast activation and matrix remodelling. Until now the type and extent of such reactions to give optimal integration of various biomaterials are practically unknown. Three principal fields of research can yield useful data to understand these phenomena better: studies on explanted biomaterials, animal models and relevant in vitro techniques. This paper will present examples of the latter field and the application of endothelial cell (EC) culture systems to study the effects of important tissue (e.g. pro-inflammatory cytokines, chemokines) and material (e.g. metal ions, particulate debris) factors on the regulation of the inflammatory and angiogenic response. A central feature is the use of microvascular endothelial cells (MEC), which can be used in both 2-and 3-dimensional (3-D) assays. We have also used genetic manipulation to develop a permanent MEC line from the human lung (HPMEC-ST1), which is being tested for its suitability to study cell-biomaterial interactions. In addition, suitable in vitro techniques are being developed in order to investigate drug delivery systems (DDS). Of particular interest is the targeting of the central nervous system, our approach being to establish a human model of the blood-brain barrier (BBB). A mainstay of our scientific philosophy is that such in vitro methods can make an important contribution to understanding biological reactions at the tissue-biomaterial interface and thus further a causal approach to tissue engineering (TE) and drug delivery applications.

Animals↗
PubMed2001

Endosonography of insulin-secreting and clinically non-functioning neuroendocrine tumors of the pancreas: criteria for benignancy and malignancy.

OBJECTIVE: Endosonography is a powerful tool in the diagnosis of gastroenteropancreatic neuroendocrine tumors. This study was performed in order to characterize endosonographic criteria of malignant and benign neuroendocrine pancreatic tumors focussing on those typically presented to endocrinologists, i.e. insulin-secreting tumors and clinically non-functioning tumors in MEN-1. DESIGN: We studied six benign insulinomas, four hormone inactive benign neuroendocrine adenomas in MEN-1, and three non-metastatic neuroendocrine carcinomas with clinically symptomatic insulin secretion. METHODS: Endosonography was performed using Pentax FG 32 UA endosonoscope with a longitudinal 7.5 MHz sector array. RESULTS: Tumor diameter was larger in malignant tumors (19 - 70 / 47.0 +/- 25.9 mm) than in benign lesions (2.3 - 19 / 9.7 +/- 5.8 mm). Hypoechoic echogeneity was more or less present in benign and in malignant tumors and could not be used as a criteria for differential diagnosis. Heterogeneous or multinodular structure on endosonographic imaging however, was an exclusive feature of malignant tumors. Echo-free areas representing cystic transformation or necrosis and vascular invasion were additional signs of malignancy. CONCLUSIONS: Molecular genetic diagnosis of MEN-1 and new therapeutic developments such as endoscopic surgery make sufficient imaging procedures in the management of neuroendocrine pancreatic tumors mandatory. Besides valid detection and exact localization, endosonography provides criteria for benign and malignant tumors and thus may be helpful in planning therapeutic strategies.

Carcinoma, Neuroendocrine↗
PubMed2001

c-erbB-2 expression in small-cell lung cancer is associated with poor prognosis.

Small-cell lung cancer (SCLC) carries a bad prognosis despite good initial response to chemotherapy. It is therefore important to identify molecular markers that influence survival as potential new therapeutic targets. In our study, expression of the tyrosine kinase c-erbB-2 (HER2/neu) receptor in tumor tissues of 107 consecutive newly diagnosed patients with primary SCLC was quantified using a monoclonal antibody directed against the c-terminal domain of c-erbB-2. A clear-cut positive expression of c-erbB-2 was observed in 13% of patients. Surprisingly, c-erbB-2 was an independent prognostic factor (RR = 2.16; p = 0.014) when a proportional-hazard model was adjusted to stage (limited vs. extensive disease) and performance status (WHO I-IV), the most relevant clinical parameters. Similarly, a significant association between c-erbB-2 and survival was obtained if a larger number of clinical parameters were included into the analysis, namely response to chemotherapy, TNM stage, lactate dehydrogenase (LDH), neuron-specific enolase (NSE), gender and age (p = 0.033). Interestingly, c-erbB-2 expression was more relevant for patients with advanced tumors. In the subgroup of patients with bad performance status (WHO II-IV), median survival of patients with undetectable c-erbB-2 expression was 274 days compared with only 23 days for patients with clear-cut positive c-erbB-2 immunohistochemistry (p = 0.0031; log-rank test). Similar results were obtained for patients with extensive disease (p = 0.028) and high TNM stages (T>2 or N>1 or M1; p < 0.068, all comparisons). In contrast, c-erbB-2 expression was not associated with survival in patients with limited disease (p = 0.97), low TNM stages (p > 0.56, all comparisons) and good performance status (p = 0.97). In conclusion, c-erbB-2 is expressed in more than 10% of SCLC. Expression of c-erbB-2 is an independent prognostic factor of survival. The effect of c-erbB-2 expression seems to become more important in advanced stages of the disease. Since c-erbB-2 is a therapeutical target in other types of cancer, further studies to identify the role of c-erbB-2 in SCLC are clearly warranted.

Age Factors↗
PubMed2001

Release of non-neuronal acetylcholine from the human placenta: difference to neuronal acetylcholine.

The synthesis and release of non-neuronal acetylcholine, a widely expressed signaling molecule, were investigated in the human placenta. This tissue is free of cholinergic neurons, i.e. a contamination of neuronal acetylcholine can be excluded. The villus showed a choline acetyltransferase (ChAT) activity of 0.65 nmol/mg protein per h and contained 500 nmol acetylcholine/g dry weight. In the absence of cholinesterase inhibitors the release of acetylcholine from isolated villus pieces amounted to 1.3 nmol/g wet weight per 10 min corresponding to a fractional release rate of 0.13% per min. The following substances did not significantly modify the release of acetylcholine: oxotremorine (1 microM), scopolamine (1 microM), (+)-tubocurarine (30 microM), forskolin (30 microM), ouabain (10 microM), 4alpha-phorbol 12,13-didecanoate (1 microM) and tetrodotoxin (1 microM). Removal of extracellular calcium, phorbol 12,13-dibutyrate (1 microM) and colchicine (100 microM) reduced the acetylcholine release between 30% and 50%. High potassium chloride (54 mM and 108 mM) increased the acetylcholine release slightly (by about 30%). A concentration of 10 microM nicotine was ineffective, but 100 microM nicotine enhanced acetylcholine release gradually over a 50-min period without desensitization of the response. The facilitatory effect of nicotine was prevented by 30 microM (+)-tubocurarine. Inhibitors of cholinesterase (physostigmine, neostigmine; 3 microM) facilitated the efflux of acetylcholine about sixfold, and a combination of both (+)-tubocurarine (30 microM) and scopolamine (1 microM) halved the enhancing effect. In conclusion, release mechanisms differ between non-neuronal and neuronal acetylcholine. Facilitatory nicotine receptors are present which are activated by applied nicotine or by blocking cholinesterase. Thus, cholinesterase inhibitors increase assayed acetylcholine by two mechanisms, protection of hydrolysis and stimulation of facilitatory nicotine receptors.

Acetylcholine↗
PubMed2001

Generation of human pulmonary microvascular endothelial cell lines.

The limited lifespan of human microvascular endothelial cells in cell culture represents a major obstacle for the study of microvascular pathobiology. To date, no endothelial cell line is available that demonstrates all of the fundamental characteristics of microvascular endothelial cells. We have generated endothelial cell lines from human pulmonary microvascular endothelial cells (HPMEC) isolated from adult donors. HPMEC were cotransfected with a plasmid encoding the catalytic component of telomerase (hTERT) and a plasmid encoding the simian virus 40 (SV40) large T antigen. Cells transfected with either plasmid alone had an extended lifespan, but the cultures eventually entered crisis after several months of proliferation. Only those cells that were transfected with both plasmids acquired the capacity to grow in vitro without demonstrating major crisis, and these cells have been in culture for 24 months. HPMEC isolated from two different donors were used, generating two populations of immortalized cells, HPMEC-ST1 and HPMEC-ST2. Single cell-derived clones of the immortalized cells HPMEC-ST1 exhibited growth characteristics that were similar to those of the parental HPMEC. One selected clone, HPMEC-ST1.6R, displayed all major constitutively expressed and inducible endothelial phenotypic markers, including platelet endothelial cell adhesion molecule (PECAM-1, CD31), von Willebrand factor (vWF), and the adhesion molecules, intercellular adhesion molecule (ICAM-1), vascular adhesion molecule (VCAM-1), and E-selectin. In addition, an angiogenic response was demonstrated by sprout formation on a biological extracellular matrix (Matrigel). The HPMEC-ST1.6R cells did not form tumors in nude mice. The microvascular endothelial cell line, HPMEC-ST1.6R, will be a valuable tool for the study of microvascular endothelial physiology and pathology including gene expression, angiogenesis, and tumorigenesis.

Adult↗
PubMed2001

Release of non-neuronal acetylcholine from the isolated human placenta is mediated by organic cation transporters.

1. The release of acetylcholine was investigated in the human placenta villus, a useful model for the characterization of the non-neuronal cholinergic system. 2. Quinine, an inhibitor of organic cation transporters (OCT), reduced acetylcholine release in a reversible and concentration-dependent manner with an IC(50) value of 5 microM. The maximal effect, inhibition by 99%, occurred at a concentration of 300 microM. 3. Procaine (100 microM), a sodium channel blocker, and vesamicol (10 microM), an inhibitor of the vesicular acetylcholine transporter, were ineffective. 4. Corticosterone, an inhibitor of OCT subtype 1, 2 and 3 reduced acetylcholine in a concentration-dependent manner with an IC(50) value of 2 microM. 5. Substrates of OCT subtype 1, 2 and 3 (amiloride, cimetidine, guanidine, noradrenaline, verapamil) inhibited acetylcholine release, whereas carnitine, a substrate of subtype OCTN2, exerted no effect. 6. Long term exposure (48 and 72 h) of villus strips to anti-sense oligonucleotides (5 microM) directed against transcription of OCT1 and OCT3 reduced the release of acetylcholine, whereas OCT2 anti-sense oliogonucleotides were ineffective. 7. It is concluded that the release of non-neuronal acetylcholine from the human placenta is mediated via organic cation transporters of the OCT1 and OCT3 subtype.

Acetylcholine↗
PubMed2001

Differential adhesion of polymorphous neutrophilic granulocytes to macro- and microvascular endothelial cells under flow conditions.

OBJECTIVE: As one of the important active barriers in the human organism, endothelial cells (EC) play a central role in the biological reaction to a variety of stimuli, e.g. during the induction and regulation of inflammation, as well as in the reaction to transplantation and biomaterial implantation. In the study of endothelial function, the most widely used in vitro model is that of human umbilical vein EC (HUVEC), i.e. an EC type of embryonic and macrovascular origin. However, many of the important pathological processes occur at microvascular level, thus questioning the validity of the HUVEC model. Moreover, the morphological and functional heterogeneity of the endothelium in the various organs, e.g. kidney, liver and lung, must be taken into consideration. The purpose of the present study was to use a dynamic cell culture system to compare the reactions of HUVEC and human pulmonary microvascular EC (HPMEC) to pro-inflammatory stimulation. METHODS: HUVEC and HPMEC in monolayer culture were stimulated by tumor necrosis factor-alpha (TNFalpha) in a parallel-plate flow chamber. Short- (4 h) and long-term (12 h) stimulation were compared. As a functional parameter, the adhesion of human peripheral blood polymorphonuclear granulocytes (PMN) to EC was quantitated both under venous and arterial flow conditions. RESULTS: Short-term (4 h) TNFalpha stimulation and venous flow conditions elicited a 32% higher PMN adhesion to HPMEC compared with HUVEC, whereas under arterial flow conditions no statistically significant differences were found. Following longer-term (12 h) TNFalpha stimulation, PMN adhesion to HPMEC was 65% higher than to HUVEC under venous flow. Under arterial flow no differences were detected. CONCLUSION: The present results provide new data on the heterogeneity of the endothelium and affect a central element in microvascular pathology, namely granulocyte-endothelial interactions. Moreover, this paper emphasizes the necessity to evaluate the in vitro models of the endothelium with respect to the extrapolation to the situation in vivo.

Cell Adhesion↗
PubMed2001

The biological role of non-neuronal acetylcholine in plants and humans.

Acetylcholine, one of the most exemplary neurotransmitters, has been detected in bacteria, algae, protozoa, tubellariae and primitive plants, suggesting an extremely early appearance in the evolutionary process and a wide expression in non-neuronal cells. In plants (Urtica dioica), acetylcholine is involved in the regulation of water resorption and photosynthesis. In humans, acetylcholine and/or the synthesizing enzyme, choline acetyltransferase, have been demonstrated in epithelial (airways, alimentary tract, urogenital tract, epidermis), mesothelial (pleura, pericardium), endothelial, muscle and immune cells (granulocytes, lymphocytes, macrophages, mast cells). The widespread expression of non-neuronal acetylcholine is accompanied by the ubiquitous expression of cholinesterase and acetylcholine sensitive receptors (nicotinic, muscarinic). Both receptor populations interact with more or less all cellular signalling pathways. Thus, non-neuronal acetylcholine can be involved in the regulation of basic cell functions like gene expression, proliferation, differentiation, cytoskeletal organization, cell-cell contact (tight and gap junctions, desmosomes), locomotion, migration, ciliary activity, electrical activity, secretion and absorption. Non-neuronal acetylcholine also plays a role in the control of unspecific and specific immune functions. Future experiments should be designed to analyze the cellular effects of acetylcholine in greater detail and to illuminate the involvement of the non-neuronal cholinergic system in the pathogenesis of diseases such as acute and chronic inflammation, local and systemic infection, dementia, atherosclerosis, and finally cancer.

Acetylcholine↗
PubMed2001

The non-neuronal cholinergic system in the endothelium: evidence and possible pathobiological significance.

An increasing body of knowledge indicates that the cholinergic system is not confined to the nervous system, but is practically ubiquitous. The present paper will address the question of the non-neuronal cholinergic system in vascular endothelial cells (EC). In tissue sections of human skin, immunohistochemical studies using confocal laser scanning microscopy showed ChAT (choline acetyltransferase) activity in the EC of dermal blood vessels. Positive ChAT immunoreactivity was also demonstrated in monolayer cultures of human umbilical vein EC (HUVEC) and a human angiosarcoma EC line (HAEND). That the synthesizing enzyme is not only present in EC, but also active was shown by measuring ChAT activity. Thus, in HUVEC cultures, ChAT activity amounted to 0.78 +/- 0.15 nmol x mg protein(-1) x h(-1) (n = 3), but was only partially (about 50%) inhibited by the ChAT inhibitor bromoacetylcholine (30 microM). In HPLC measurements, a concentration of 22 +/- 2 pmol acetylcholine (ACh) per 10(6) cells was found (n = 6). However, using a cholinesterase-packed analytical column to check the identity of the acetylcholine peak, the peak height was found to be reduced, although a significant peak still remained, indicating the existence of a compound closely related to ACh. Further immunocytochemical experiments indicated that EC in vitro also express the vesicular acetylcholine transporter (VAChT) system. Preliminary immunoelectron microscopic studies suggest a topographical association of VAChT with endothelial endocytotic vesicles. The presented experiments clearly demonstrate the existence of essential elements of the cholinergic system (ChAT, VAChT, ACh) in the human endothelium. The biological functions of ACh synthesized by endothelial cells are the focus of ongoing research activity.

Acetylcholine↗
PubMed2000

Microcirculatory dysfunction in sepsis: a pathogenetic basis for therapy?

Sepsis is a frequent complication of multiple organ dysfunction syndrome and remains a major problem of intensive care medicine. It is also a common factor in the final cause of death in hospital populations. Clinical observations, assisted by invasive monitoring techniques as well as pathological-anatomical studies, clearly indicate that microcirculatory dysfunction lies at the centre of sepsis pathogenesis. Numerous animal models, from rodents to primates, many of which employ bacteria or their toxins, especially endotoxins, have helped to shed light on the pathomechanisms leading to this dysregulation in the peripheral circulation. Among these are activation of humoral and cellular inflammatory mediator systems, with special emphasis on neutrophil-endothelial interactions, affecting endothelial barrier function and vasoregulation and ultimately leading to severely perturbed oxygen transport and utilization. In vitro studies have provided more insight into the molecular mechanisms involved in this microcirculatory dysfunction, although much more attention must be directed towards microvascular endothelial cells and the role of heterogeneity of response in various vascular beds. These experimental data must in turn be validated by comparing with the human in situ situation, both clinical and morphological. This review aims at a critical appraisal of the clinical and experimental evidence for sepsis-induced dysregulation of the microcirculation and how knowledge of the underlying cellular and molecular pathology could be used to make therapy more rational and effective. To date, therapeutic approaches, such as anti-cytokine and anti-oxidant regimens, which have been highly successful in experimental models, have failed to demonstrate clinical efficacy. Newer approaches, such as targeting the coagulation system, nitric oxide synthesis or intracellular signal transduction, are also discussed. The necessity to focus on the role of anti-inflammatory mediators, as well as the pathogenetic significance of important molecular groups, such as the heat shock proteins, which until now have been given scant attention, will be stressed.

Animals↗
PubMed2000

[Calciphylaxis: ischemic tissue necrosis in chronic renal failure. Case report and review of the literature].

Calciphylaxis is a rare but potentially life-threatening complication in chronic renal failure. It is characterized by ischemic tissue necrosis primarily of the skin. The typical histopathologic finding is microvascular calcification with endovascular fibrosis. Patients typically present with violaceous, mottled and painful lesions which tend to progress to non-healing ulcers and necrosis. Most frequently the lower extremities are involved in a symmetric fashion but the trunk may also be affected. Sepsis from superinfection of the lesions accounts for the high mortality of this disease which is of importance for dermatologists and nephrologists alike. 61-year-old female patient developed lesions of calciphylaxis on both calves two years after beginning hemodialysis to treat renal failure due to diabetic glomerulosclerosis. We discuss aspects of the pathogenesis of calciphylaxis, as well as diagnosis, treatment and means of prevention, and review the current literature.

Biopsy↗
PubMed2000

[A case report: suppurative pericardial effusion].

We present the case of a 67 year old woman who was resuscitated due to cardiac tamponade. Examination of the pus fluid showed a bacterial infection with streptococcus milleri. Four days before resuscitation the patient experienced weakness, dyspnoea, increased temperature (39 degrees C), swelling of the neck, and pain on swallowing. Using computed tomography, examination revealed an infection extending from the right tonsil to the mediastinum and into the pericardium. After surgery to remove the retropharyngeal abscess, the patient healed well. Therefore, on presentation of a cardiac tamponade, possible hematogenous or lymphogenous causes or per continuitatem infections should always be considered. In this case the germs in the fluid and the typical patient history indicated an oropharyngeal reason.

Aged↗
PubMed2000

Biomaterial-induced sarcoma: A novel model to study preneoplastic change.

In the study of carcinogenesis most interest has focused on carcinomas, as they represent the majority of human cancers. The recognition of the adenoma-carcinoma sequence both in humans and in animal experimental models has given the field of basic oncology the opportunity to elucidate individual mechanisms in the multistep development of carcinoma. The relative scarcity of human sarcomas coupled with the lack of adequate animal models has hampered understanding of the molecular genetic steps involved. We present an experimental model in the rat in which a high incidence of malignant mesenchymal tumors arise around a subcutaneously implanted biomaterial. Nine commercially available biomaterials were implanted in a total of 490 rats of the Fischer strain for 2 years. On average, macroscopic tumors were found in 25.8% of implantation sites over a period from 26 to 110 weeks after implantation. The most frequent tumors were malignant fibrous histiocytomas and pleomorphic sarcomas, although fibrosarcomas, leiomyosarcomas, and angiosarcomas readily developed, the latter especially around polyurethane implants. Of particular interest are the results of a detailed histological study of the capsules around the implanted biomaterials without tumors. Here a spectrum of change from focal proliferative lesions through preneoplastic proliferation to incipient sarcoma could be observed. A parallel immunohistochemical study of peri-implant capsules showed that proliferating cell nuclear antigen was of particular help in identifying these atypical proliferative lesions. To our knowledge this is the first description of a sarcoma model in which preneoplastic lesions can be readily identified and also reproducibly induced. This model provides the molecular biologist with defined stages in the development of mesenchymal malignancy, with which the multistage tumorigenesis hypothesis can be tested, analogous to the well-known adenoma-carcinoma sequence.

Animals↗
PubMed2000

Inhibin-alpha CD99, HEA125, PLAP, and chromogranin immunoreactivity in testicular neoplasms and the androgen insensitivity syndrome.

We investigated 115 testicular and 3 epididymal tumors and 6 cases of the complete androgen insensitivity syndrome (AIS) for the expression of inhibin-alpha, CD99, HEA125, PLAP, and chromogranin, using monoclonal antibodies and standard immunhistochemical techniques. Ihibin-alpha was detected in the neoplastic cells in 27 of 27 primary Leydig cell tumors (LCTs), 1 of 1 metastatic LCT, 6 of 20 Sertoli cell tumors (SCTs), 4 of 5 juvenile granulosa cell tumors (GCTs), and 2 of 5 unclassified sex cord-stromal tumors (USCSTs). Except for 2 choriocarcinomas, the choriocarcinomatous component of 1 mixed germ cell tumor, and a small focus of inhibin-positive syncytiotrophoblast in 1 embryonal carcinoma, inhibin-a immunoreactivity was not present in the neoplastic cells of the 38 remaining testicular germ cell tumors; 11 B-cell and 1 T-cell lymphomas; 1 granulocytic sarcoma; and 1 rhabdomyosarcoma of the testis; 1 adenoma of the rete testis, and 3 adenomatoid tumors of the epididymis. Inhibin-alpha immunoreactivity was present in the Sertoli cells and Leydig cells in 5 testicular hamartomas and in 1 Sertoli cell adenoma in 6 cases of AIS; both Sertoli and Leydig cells were also positive in the extranodular testicular parenchyma present in 2 of these cases. CD99 was detected in 10 of 15 primary LCTs, 1 of 7 SCTs, 3 of 5 JGCTs, and in 1 of 5 USCSTs but was not found in any tumor outside the sex cord-stromal category. HEA125 immunostaining was not detected in sex cord-stromal tumors; however, 3 of 12 seminomas, 3 of 12 embryonal carcinomas, 6 of 8 yolk sac tumors, and 1 of 2 teratomas were HEA125 positive. PLAP was not detected in sex cord-stromal tumors except for 4 of 15 primary LCTs but was present in most germ cell tumors. Chromogranin immunostaining was present in the sex cord-like element in 1 of 5 USCSTs, 1 of 8 YSTs, 1 of 2 teratomas, and in 1 of 1 rete adenoma, and in normal adjacent rete testis. In conclusion, although inhibin-alpha and PLAP, and, to a somewhat lesser extent, CD99 and HEA125 immunostaining are helpful in the differential diagnosis of certain testicular neoplasms that are difficult to distinguish on morphologic grounds, chromogranin is far less helpful in this context.

12E7 Antigen↗
PubMed1999

Remodeling of peritoneal-like structures by mesothelial cells: its role in peritoneal healing.

BACKGROUND: Intraabdominal adhesions are a common complication following laparotomy. Since the exact mechanisms involved in this processes are unknown we have analyzed in vitro the role of mesothelial cells in peritoneal healing. MATERIAL AND METHODS: Human mesothelial cells from omental tissue were cultivated for 2 weeks in a three-dimensional culture either on or in a collagen type I matrix. The effects of blood and collagen matrix were analyzed by exposing mesothelial cells to an overlying blood clot, simulating intraperitoneal bleeding, or a second collagen layer. The production of collagen types III and IV, fibronectin, and laminin was analyzed with immunohistochemical methods. RESULTS: Mesothelial cells grown on a collagen matrix formed a monolayer of flat or cobblestone-like cells whereas those cultivated in a collagen matrix exhibited spindle-like morphology. Mesothelial cells failed to grow into an overlying collagen matrix, but did grow into a blood clot, emphasizing a potential role of blood clots in peritoneal adhesion formation. Independent of the culture systems mesothelial cells produced collagen type III, fibronectin, and laminin but not collagen type IV. CONCLUSIONS: Our experiments demonstrate remodeling of peritoneal-like structures by mesothelial cells in a three-dimensional culture reflecting their putative role in the reepithelialization after serosal defects, and also in the formation of peritoneal adhesions.

Cells, Cultured↗