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Biomedical subjects

P Reinecke

Publications and source records attributed to P Reinecke.

At least 19 recordsLinked to original sources

Multifocal epithelioid hemangioendothelioma: case report of a clinical chamaeleon.

Epithelioid hemangioendothelioma is an extremely rare vascular bone tumor with a slow growth and poor prognosis. The term was designed to describe neoplasms that had an appearance in between hemangiomas and sarcomas. Various synonyms for epithelioid hemangioendothelioma are used clinically: low grade anaplastic angiosarcoma, cellular hemangioma, histiocytoid hemangioma and angioendothelioma. However, it represents 1% of all vascular neoplasms and is locally aggressive. We report the course of disease of a 47-year-old man who presented to our clinic with unspecific abdominal and back pain. Radiological findings revealed multiple lesions in the spine as well as liver and spleen involvement. Tumor histology of the bone and liver biopsies confirmed the diagnosis of epithelioid hemangioendothelioma. Although treatment was initiated with thalidomide, the patient developed multiple organ dysfunction syndrome (MODS) and succumbed to his disease. This case report may contribute to the data on clinical findings and natural history of this rare tumor.

Angiogenesis Inhibitors↗

[Bilateral large conjunctival tumours as primary manifestation of sarcoidosis--successful treatment with steroid-depot-injections].

INTRODUCTION: Ocular manifestations of sarcoidosis vary enormously. They include the conjunctiva, lacrimal gland, orbita, intraocular structures and eye-lid, either isolated or combined. We describe a female patient who presented with unusually large, bilateral conjunctival tumours as a primary manifestation of sarcoidosis. PATIENT: A 79-year-old white woman was referred to us for further management of a persisting "conjunctivitis", which had been refractory to treatment with multiple medications. Initial examination disclosed swollen eye-lids and bilateral large hard tumours of the inferior fornix. The obtained brush smear, which was cytopathologically evaluated, revealed epitheloid cells and multinucleate giant cells. After 4 weeks she developed three reddish-brown maculopapular lesions on her face. The subsequent biopsy from the left inferior fornix and the skin showed histopathologically a granulomatous epitheloid cell inflammation without central necrosis and without acid-proof bacilli. Therefore a sarcoidosis was included into the differential diagnosis. The systemic evaluation revealed no other manifestation. At first we tried to reduce the chronically inflammatory tumours with different immunomodulating local treatment forms. Only the repeated intralesional injection of a steroid depot showed a complete disappearance of all conjunctival and skin tumours. CONCLUSION: An isolated bilateral primary manifestation of sarcoidosis with large massive conjunctival tumours is very rare and clinically not typical. The non-invasive, cytopathological examination by means of brush smears offers a new perspective in the fast diagnosis of conjunctival manifestation of sarcoidosis. The tumours respond excellently to the intralesional injection of steroid depots.

Aged↗

Analysis of properdin (BF) genotypes associated with litter size in a commercial pig cross population.

Properdin (BF) was investigated as a candidate gene influencing litter size in a commercial pig cross population. The BF gene was chosen because of its integral role in influencing uterine epithelium growth and because several quantitative trait loci (QTL) with impact on reproductive traits have been detected near the centromere of porcine chromosome 7. A total of 123 F2 (Large White x Landrace) x Leicoma sows were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The sows were divided into two extreme performance groups, one with a high litter size (n = 61, > or = 14.3 piglets per litter) and the other with a low litter size (n = 62, < or = 11.3 piglets per litter). Although genotype and allele frequencies were uneven with 2.4% (AA), 16.3% (AB), 81.3% (BB) and 0.11 (A): 0.89 (B), the allele A was the unfavourable one, leading to less offspring. With regard to the level of significance at p < 0.05, the total number of born (TNB) and number of born alive (NBA) piglets were associated with BF genotypes. The genotype AA led to 10.55 TNB and 10.00 NBA, whereas the genotype BB led to 13.19 TNB and 12.11 NBA. The genotype AB was intermediate. In future, a systematic mating test is necessary in order to obtain more balanced genotype frequencies. Furthermore, it should be taken into consideration that the investigated polymorphism is located in an intronic region and the causative mutation is not clear yet.

Animals↗

[Homologous vein transplantation in cruropedal arterial reconstruction].

Allogenic venous transplantation represents an alternative procedure for preventing leg amputation. This study reviewed the question of whether immunologic monitoring and immunosuppressive therapy provide results close to those of autologous reconstructions. Twenty-eight patients received 31 homologous venous transplants. The average age in this group of 15 women and 13 men was 64.5 years. Limbs in danger of amputation could be kept longer in two thirds of them. These promising results show the superiority of this method over the use of alloplastic material in regions with cruropedal vessels. Therefore, it can be recommended in acute leg ischemia with lack of autologous vascularity. Improving guidelines for indication will be an interesting research field, and more contributions are needed.

Adult↗

[Mycotic visceral artery aneurysm: clinical picture, diagnosis, differential therapy, and discussion of the literature].

Bacterially infected arterial aneurysms were named mycotic aneurysms by William Osler in 1885 due to their morphology. This rare vascular disease is mainly localized in the femoral artery but also occurs in the aorta and visceral arteries. After the first surgically treated mycotic visceral aneurysm in 1949, we found 36 casuistics in the literature. We report on two patients treated in our department with mycotic visceral aneurysms and discuss the literature concerning topography, differential diagnosis, and surgical management.

Adult↗

Disseminated microvascular pulmonary tumor cell embolism: a rare cause of fulminant pulmonary hypertension.

BACKGROUND: Disseminated pulmonary tumor embolization is a rare cause of pulmonary hypertension and is often diagnosed only after the patient has died. CASE REPORT: We report on a 41-year-old male who was admitted because of severe dyspnea and tachycardia. Contrast enhanced spiral computed tomography did neither establish pulmonary thromboembolism nor pulmonary metastasis. Right heart catheterization revealed severe pulmonary hypertension (pulmonary vascular resistance (PVR) 678 dyn x sec x cm(-5)). PVR did not respond to therapy with intravenous nitrate or inhaled iloprost in this critically ill patient. 2 days after admission, the patient died because of refractory right heart failure. Autopsy revealed microscopic pulmonary tumor embolism due to a metastasizing adenocarcinoma of the pancreas. CONCLUSION: Disseminated tumor cell embolism should be considered as a rare differential diagnosis in patients with refractory pulmonary hypertension.

Adenocarcinoma↗

Chemotherapeutic potential of plant alkaloids and multidrug resistance mechanisms in malignant fibrous histiocytoma of the heart.

Primary malignant fibrous histiocytoma (MFH) of the heart is a rare and highly malignant soft tissue tumor, which is largely resistant to conventional chemotherapy and radiotherapy. Therefore, we analyzed growth inhibitory effects of different chemotherapeutic agents and mechanisms of drug resistance in the recently established cell line MFH-H derived from a human primary cardiac MFH. The growth inhibitory effects of etoposide, vincristine, and paclitaxel were tested using the MTT assay. The expression and function of multidrug resistance-related proteins, i.e. the P-glycoprotein, the multidrug resistance-associated protein (MRP) and the lung resistance-related protein (LRP) were determined by FACScan and functional assays of cellular drug efflux. The concentration required for a 50% inhibition of growth (IC50) was 0.001 microM for etoposide and 0.035 microM for vincristine. Paclitaxel dissolved in Cremophor EL/ethanol inhibited the cell growth of MFH-H cells more intensively (IC50: 0.27 microM) than paclitaxel dissolved in DMSO (IC50: 11.09 microM) suggesting that Cremophor EL is contributing to the inhibitory effects of paclitaxel. The response of MFH-H to etoposide, vincristine and paclitaxel/Taxol could not be predicted by the expression and function of P-glycoprotein, MRP and LRP. This study demonstrates that etoposide and to a lesser extent vincristine can effectively inhibit the growth of MFH-H cells, irrespective of the multidrug resistance phenotype. MFH-H cells are relatively insensitive to paclitaxel dissolved in DMSO, in contrast to paclitaxel dissolved in Cremophor EL/ethanol indicating that the diluent Cremophor contributes to the antiproliferative effects of the taxane paclitaxel.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Postarthroplasty histiocytic lymphadenopathy in a patient with uterine carcinoma.

INTRODUCTION: Postarthroplasty histiocytic lymphadenopathy is a benign reactive sinus histiocytosis. CASE REPORT: We report on the case of a 68-year-old woman presenting with pelvic postarthroplasty histiocytic lymphadenopathy after hysterectomy because of uterine carcinoma. CONCLUSION: This unusual form of histiocytic lymphadenopathy should be included in the differential diagnosis of gynecologic oncology patients who have had joint replacements to avoid misdiagnosis of a neoplasm.

Aged↗

Fabry disease in patients with hypertrophic cardiomyopathy (HCM).

Fabry disease is an X-linked recessive lysosomal storage disorder with variable phenotype characterized by the accumulation of glycosphingolipid in various tissues. Unlike patients with the classical systemic Fabry disease entity, who present with multiple organ involvement, patients with a cardiac variant of Fabry disease are characterized mainly by myocardial hypertrophy. Therefore, the cardiac variant of Fabry disease may be defined as a cardiomyocytic storage disorder, thus, mimicking the clinical features of hypertrophic obstructive and especially non-obstructive cardiomyopathy. In patients with unexplained left ventricular hypertrophy the diagnosis of a cardiac variant of Fabry disease is performed by light- and electron microscopic evaluation of endomyocardial catheter biopsy specimens and/or serologic investigations (decreased activity of alpha-galactosidase A in plasma or leucocytes). Several studies show that between 4% and 8% of unselected patients with the clinical features of hypertrophic non-obstructive cardiomyopathy have a cardiac variant of Fabry disease. In each patient with unexplained myocardial hypertrophy concealed myocardial storage disease, especially cardiac Fabry disease has to be considered and should be ruled out or confirmed by endomyocardial catheter biopsy. This is important because of the recently reported alpha-galactosidase A enzyme replacement therapy in Fabry disease. Randomized, multicenter studies are mandatory to test the hypothesis that enzyme replacement therapy leads to a beneficial clinical effect in the cardiac variant form of Fabry disease and may prevent the progression of the disease in asymptomatic patients.

Aged↗

[Circular hemorrhagic subendocardial necrosis after heart arrest and resuscitation].

A 19 year old boy, previously healthy suffered a cardiac arrest by getting up. Ten minutes afterwards the general practitioner commenced cardiopulmonary resuscitation, 15 minutes later ventricular fibrillation developed and the emergency physician carried out intubation and repeated defibrillation. During the next few hours a stabilization of the circulatory system was achieved. Five days after the cardiac arrest brain death occurred. The postmortem findings on the heart (only a heart section was performed) showed extensive circular hemorrhagic subendocardial necrosis with initial organization of the left ventricular wall and the septum with a well-preserved subendocardial area. In the right ventricular wall only a few small areas of organization were observed. All lesions were consistent with the cardiac arrest suffered 5 days previously. The morphological changes differ from those of a usual hemorrhagic infarction and of the sequences of a cardiopulmonary resuscitation. The circular subendocardial necroses occur after a cardiac arrest which exceeds the resuscitation time of the heart. They do not respect the area of coronary distribution and their hemorrhagic component develops after successful reanimation within the necrotic myocardium.

Adult↗

Secretion of GM-CSF and M-CSF by human renal cell carcinomas of different histologic types.

OBJECTIVES: To analyze the secretion of hematopoietic growth factors and the expression of their corresponding receptors in 40 newly established renal cell carcinoma (RCC) cell lines of different histologic types. Little is known about the secretion and function of hematopoietic growth factors by human RCCs. METHODS: The expression of the hematopoietic growth factors (ie, erythropoietin, interleukin [IL]-3, IL-5, granulocyte colony-stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor [GM-CSF], and macrophage colony-stimulating factor [M-CSF]) was determined by enzyme-linked immunosorbent assay analysis under different culture conditions, including suspension culture and monolayer cultures (plastic and Matrigel-coated culture flasks). The expression of their corresponding receptors was defined by fluorescence activated cell scanner analysis and by reverse-transcriptase polymerase chain reaction. The response of the RCC cell lines to exogenous hematopoietic growth factors was analyzed by MTT assay. RESULTS: In almost all of the cell lines, significant amounts of GM-CSF and M-CSF were secreted, and in four cell lines, a secretion of G-CSF was detected. Fourteen RCC cell lines showed secretion of IL-3, and production of IL-5 and erythropoietin was not observed in any cell line. Secretion of GM-CSF and M-CSF was affected by the substratum offered for cell attachment in the adherent cultures. GM-CSF secretion was more pronounced under culture conditions with a reduced frequency of cell-to-cell contacts. Two cell lines were shown to express receptors for M-CSF, but receptors for G-CSF and GM-CSF could not be detected in any cell line. Exposure to exogenous G-CSF, GM-CSF, and M-CSF did not affect the proliferation of our RCC cell lines. CONCLUSIONS: The results of our study clearly demonstrate that human RCC cells can secrete significant amounts of G-CSF, GM-CSF, M-CSF, and IL-3, and are thereby theoretically able to modulate the host's tumor-directed immune response.

Carcinoma, Renal Cell↗

Growth inhibitory effects of paclitaxel on human epithelioid sarcoma in vitro: heterogeneity of response and the multidrug resistance phenotype.

BACKGROUND: Epithelioid sarcoma is a highly malignant soft tissue tumor that is largely resistant to conventional chemotherapy and radiotherapy. Because paclitaxel has been proven to be effective in other human malignancies refractory to conventional chemotherapy, the authors analyzed the in vitro growth inhibitory effects of paclitaxel on the human epithelioid-sarcoma cell line GRU-1 and its clonal subpopulations GRU-1A, GRU-1B, and GRU-1C. METHODS: Paclitaxel-induced morphologic alterations were visualized using light microscopy, immunofluorescence microscopy, and transmission electron microscopy. The antiproliferative effects of paclitaxel on the cell lines were determined by 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium' bromide (MTT) assay. The extent of paclitaxel-induced apoptosis was determined by light microscopy. The expression and function of P-glycoprotein and the multidrug resistance-associated protein (MRP) were defined by reverse transcriptase-polymerase chain reaction and fluorescence-activated cell sorter analysis. RESULTS: Paclitaxel-induced morphologic alterations such as micronucleus formation and microtubule bundles showed no significant differences between the parental cell line and its clonal subpopulations. A significant (P < 0.05) dose-dependent growth inhibition was observed in GRU-1 and its clonal subpopulations, with the IC(50) (concentration that inhibits 50%) values ranging from 0.04-0.49 microM in the different subpopulations. Paclitaxel-induced growth inhibition was accompanied by a slight increase in apoptosis. All cell lines showed an expression of and an effective function of P-glycoprotein and MRP. CONCLUSIONS: The differential response of GRU-1 and its clonal subpopulations to paclitaxel could not be predicted by the expression and function of P-glycoprotein and MRP, suggesting that other drug resistance mechanisms might be relevant in the heterogenous response observed in the epithelioid sarcoma cell lines in the current study.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Differential response to transforming growth factor (TGF)-alpha and fibroblast growth factor (FGF) in human renal cell carcinomas of the clear cell and papillary types.

The clear cell and the papillary types of human renal cell carcinoma (RCC) are distinct tumour entities with marked differences in their biological properties. Because growth factors are considered to affect profoundly the biological behaviour of malignant tumours, we compared the expression and function of transforming growth factor (TGF)-alpha and fibroblast growth factor (FGF) in both types of RCCs. Both in vivo and in vitro expression of TGF-alpha, epidermal growth factor-receptor (EGF-R), FGF-2 and FGF type 3- and 4-receptors was found in RCCs of both types. However, marked differences between clear cell and papillary RCCs became evident for TGF-alpha secretion, which could be demonstrated in 20 out of 24 (83%) clear cell RCCs but in only two out of four (50%) papillary tumours. Moreover, the mean TGF-alpha secretion rate in clear cell RCCs significantly (P<0. 05) exceeded that of papillary RCCs. Because the expression of growth factor receptors could not prove the corresponding signalling cascades were functional, tumour cell proliferation was tested after exposure to exogenous TGF-alpha or FGF-1. These experiments demonstrated that papillary RCCs did not respond significantly to exogenous TGF-alpha or FGF-1, whereas eight (33%) (TGF-alpha) and 11 (46%) (FGF-1) out of 24 clear cell RCCs responded with significant (P<0.05) growth stimulation. In conclusion, our investigation presents data indicating that TGF-alpha and FGF are functionally involved in the progression of clear cell RCCs, directly stimulating proliferation by autocrine and/or paracrine actions. In contrast, TGF-alpha and FGF did not directly stimulate the proliferation of our papillary RCCs, thereby suggesting functional defects or a blockade in the corresponding signalling cascades. This differential functionality might contribute to the more aggressive behaviour of clear cell RCCs.

Adenocarcinoma, Clear Cell↗

Analysis of growth factor-dependent signalling in human epithelioid sarcoma cell lines. clues To the role of autocrine, juxtacrine and paracrine interactions in epithelioid sarcoma.

Human epithelioid sarcoma (ES) is an extremely aggressive soft tissue tumour of unknown histogenesis. Although growth factor-dependent signalling cascades significantly affect the biological behaviour of malignant tumours, little is known so far about their role in human ES. The present investigation, therefore, analyses the coexpression and function of different growth factors and their receptors in the human ES cell line GRU-1 and its clonal subpopulations (GRU-1A, GRU-1B and GRU-1C). As shown by Northern blot, flow cytometry, immunocytochemistry and MTT assay, all ES cell lines expressed transforming growth factor (TGF)-alpha and the epidermal growth factor receptor (EGF-R). Although no response to exogenous TGF-alpha was observed, antagonistic anti-EGF-R antibodies (at 20 microg/ml) induced significant (P<0.05) growth inhibition in all cell lines. All cell lines showed coexpression of platelet-derived growth factor (PDGF)-A and the corresponding receptors. Neutralisation of ES-derived PDGF by anti-hPDGF antibodies resulted in significant (P<0.05) growth inhibition of all clonal subpopulations. Although all cell lines expressed TGF-beta(1) as well as TGF-beta type I and type II receptors (TGF-BI-R and TGF-BII-R), growth inhibition (P<0.05) by exogenous TGF-beta(1) was achieved in the clonal subpopulations only and not in the parental cell line. No ES cell line expressed acidic fibroblast growth factor (FGF) but stimulation of FGF type 3 and type 4 receptors (FGF-3R and FGF-4R) by exogenous acidic FGF (aFGF) resulted in a marked (P<0.05) acceleration of proliferation in all cell lines. In conclusion, our investigation suggests an intricate network of autocrine, juxtacrine and paracrine signalling between ES tumour cells and adjacent non-neoplastic stromal cells.

Blotting, Northern↗

Multidrug resistance phenotype and paclitaxel (Taxol) sensitivity in human renal carcinoma cell lines of different histologic types.

We compared the effects of paclitaxel (Taxol) in human renal cell carcinoma (RCC) of different histologic types. The growth inhibitory effects of paclitaxel on 34 human RCC cell lines of strictly defined different histologic types were determined by 3-[4,5-dimethylthiazolyl]-2,5-diphenyltetrazoliumbromide (MTT) assays. Paclitaxel-induced morphologic alterations were visualized by light and immunofluorescence and by transmission electron microscopy. The expression and function of P-glycoprotein and multidrug resistance-associated protein (MRP) were defined by reverse transcriptase polymerase chain reaction and fluorescence-activated cell sorting (FACS) analysis, respectively. Modulation of P-glycoprotein function was performed by verapamil or Cremophor EL. A significant (p < 0.05) dose-dependent paclitaxel-induced growth inhibition could be demonstrated in all cell lines, with the effects of paclitaxel dissolved in Cremophor EL/ethanol (= Taxol) exceeding the effects of paclitaxel dissolved in dimethyl sulfoxide. The extent of response markedly varied between the different cell lines, although chromophilic RCCs exhibited a more pronounced response to Taxol (IC50: 0.03-0.38 microM) than clear cell RCCs (IC50: 0.01-36.69 microM). Exposure to paclitaxel/Taxol induced an increase of microtubule bundles in the clear cell and the chromophobe RCCs but not in the chromophilic RCCs. The expression of the MRP was low in RCC cell lines and was not found to be related to paclitaxel/Taxol sensitivity. In contrast, the expression level of P-glycoprotein was much more pronounced and showed a positive correlation (p < 0.05) with the response to paclitaxel. Reversal of P-glycoprotein function by verapamil or Cremophor EL enhanced the growth inhibitory effects of paclitaxel and further supported the role of P-glycoprotein for paclitaxel sensitivity of human RCCs. Paclitaxel/Taxol effectively inhibits proliferation of human RCCs in vitro, irrespective of their histologic types. Moreover, expression and function of P-glycoprotein markedly contribute to paclitaxel responsiveness, although other as yet undefined drug resistance mechanisms are effective in human RCCs as well.

ATP Binding Cassette Transporter, Subfamily B, Mem↗