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Biomedical subjects

P Reinecke

Publications and source records attributed to P Reinecke.

At least 37 records · Page 2Linked to original sources

Temporary remission of an alveolar rhabdomyosarcoma diagnosed and treated as acute leukemia.

A 29-year-old man with alveolar rhabdomyosarcoma was considered to be suffering from acute leukemia. A bone marrow aspirate had revealed extensive infiltration by atypical blast-like cells which were interpreted as acute lymphoblastic leukemia. Although there was no confirmation of this diagnosis by immunophenotyping chemotherapy with a protocol suited for the treatment of acute lymphoblastic leukemia was started prior to histological analysis and resulted in a complete temporary remission after the first cycle. Histological analysis of a bone marrow biopsy revealed an alveolar rhabdomyosarcoma, as further confirmed by molecular genetic analysis. Two months after the end of chemotherapy, there was an extensive recurrence and the patient died one year after initial diagnosis with chemotherapy refractory disease. In conclusion, rhabdomyosarcoma should always be included in the differential diagnosis of systemic diseases with extensive bone marrow infiltration by tumor cells which could otherwise be misinterpreted as a haematological malignancy.

Acute Disease↗

[Alveolar rhabdomyosarcoma presenting as acute leukemia].

Rhabdomyosarcoma is the most common soft tissue sarcoma in adolescence and childhood, which manifests by the locally destructive growth of the primary tumor or its metastases. We report on a 29-year-old man with an alveolar rhabdomyosarcoma presenting with an unusual leukemia-like picture. On admission, the patient suffered from diffuse bone pain and renal insufficiency. Peripheral blood analysis showed anaemia, thrombocythaemia and blast-like cells. A bone marrow aspirate revealed extensive infiltration by atypical blast-like cells which were interpreted as acute lymphoblastic leukemia. Although confirmation of this diagnosis by immunophenotyping did not succeed chemotherapy was started immediately and led to partial remission. Histologic analysis of a bone marrow biopsy from the iliac crest, however, revealed an extensive solid tumor with alveolar spaces, lined by primitive round cells with positive PAS-reaction in the cytoplasm. Immunostaining demonstrated a positive reaction of the tumor cells for desmin and in a few tumor cells for smooth-muscle-actin. Chromosomal analysis showed a t(2;13) translocation typical for alveolar rhabdomyosarcoma. Although multiple lytic lesions of the skeletal system became evident during the further clinical course, the site of origin of the primary tumor could not be defined retrospectively. In conclusion, rhabdomyosarcoma should be included in the differential diagnosis of systemic diseases with extensive bone marrow infiltration by tumor cells that could otherwise be misinterpreted as a haematologic malignancy.

Acute Disease↗

Antiproliferative effects of paclitaxel (Taxol) on human renal clear cell carcinomas in vitro.

The aim of this study was to analyse the direct antiproliferative effects of paclitaxel on 20 different renal clear cell carcinoma (RCCC) cell lines comparing the effects of paclitaxel dissolved in either DMSO or Cremophor EL/ethanol (Taxol). The MTT assay was used to determine the growth inhibition of the cell lines by paclitaxel. In addition, micronuclei and microtubule alterations were examined by light and immunofluorescence microscopy. A significant (P < 0.05) dose-dependent inhibition of proliferation was evident in 19 out of 20 cell lines after exposure to paclitaxel dissolved in DMSO and in all cell lines after exposure to paclitaxel in Cremophor EL/ethanol. The extent of response markedly varied between the different cell lines ranging from modest effects to reduction of cell viability down to 1-2% of the control. The effects of paclitaxel in Cremophor EL/ethanol proved to be more pronounced than the effects of paclitaxel dissolved in DMSO. This observation could be explained by additional growth inhibitory effects of Cremophor EL alone. Light microscopy revealed extensive micronucleus formation after treatment with paclitaxel. However, the failure to demonstrate differences of micronucleus formation in paclitaxel-responsive and non-responsive RCCC cell lines argued against a causal relationship between micronucleus formation and growth inhibition. Immunofluorescence microscopy revealed no differences in the formation of abnormal microtubules in cell lines responsive or non-responsive to the growth inhibitory effects of paclitaxel. Further investigations, therefore, are needed to understand the mechanisms determining the response of RCCCs to paclitaxel treatment.

Antineoplastic Agents, Phytogenic↗

Lymphoid myelofibrosis associated with high grade B cell lymphoma of the liver: morphological, cytogenetic, and clinical features.

Severe pancytopenia associated with moderate hepatosplenomegaly, increased serum lactic dehydrogenase (LDH) levels, and hypogammaglobulinemia were found in a young male patient. Bone marrow histology showed extensive fibrosis, hypoplasia of erythro- and granulocytopoiesis, and hyperplasia of megakaryocytopoiesis associated with histiocytic fat cell phagocytosis and infiltration of abnormal lymphocytes, compatible with lymphoid myelofibrosis. Striking chromosomal aberrations indicating karyotype evolution were also demonstrated by cytogenetic analyses (47, XY, +3 / 47, XY, +3, 1p+ / 46, XO, +3, 1p+, -Y). The clinical course was characterized by cyclic febrile episodes accompanied by excessive increase of serum LDH levels and leukocyte counts, and decrease of platelet counts, followed by spontaneous regression. Further diagnostic procedures, including two liver biopsies and computed tomography, did not detect any manifestation of lymphoma. Eventually, the patient developed rapidly progressive, lethal pulmonary aspergillosis. At autopsy, high grade B cell lymphoma of the liver was found. In this case, the lymphoid myelofibrosis seen on bone marrow biopsy may be considered as a manifestation of "discordant" bone marrow histology related to high grade lymphoma. With respect to the cyclic clinical course, a possible role of apoptotic mechanisms in the physiopathology of this disorder is reviewed.

Adult↗

Functional intactness of stimulatory and inhibitory autocrine loops in human renal carcinoma cell lines of the clear cell type.

PURPOSE: The aim of the present study was to analyze the contribution of different stimulatory and inhibitory growth factors to the deregulated proliferation of human RCCs. MATERIALS AND METHODS: The expression of different growth factors and their corresponding receptors were analyzed by Northern blot, FACS, ELISA and immunocytochemistry in 13 permanent human RCC cell lines of the clear cell type. Moreover, the functional intactness of growth factor-related signal transduction pathways was investigated. RESULTS: All RCC cell lines expressed EGF-receptor mRNA and protein and 10 cell lines secreted TGF-alpha. Exogeneously added TGF-alpha resulted in a significant (p < 0.05) stimulation of growth in 6 RCC cell lines and a significant (p < 0.05) inhibition of proliferation in 3 cell lines. PDGF B and the corresponding type beta receptor were expressed in a single cell line. mRNA expression of PDGF A and PDGF-alpha-receptor as well as IGF-1 and its receptor could not be detected in any cell line. Eleven RCC cell lines expressed TGF-beta 1 mRNA and in all cell lines TGF-beta 1 secretion into the supernatant could be demonstrated. Whereas all cell lines exhibited TGF-beta type II-receptor mRNA, type I-receptor mRNA could be detected only in 3 cell lines. TGF-beta type III-receptor was observed in 1 cell line. Exogeneously added TGF-beta1 resulted in a significant (p < 0.05) inhibition of proliferation in 7 RCC cell lines. CONCLUSION: Clear cell RCCs exhibit a complex and heterogeneous expression pattern for various growth factors and their receptors. Growth factor secretion and intact signal transduction pathways in most clear cell RCCs facilitate an intricate modulation of RCC growth by autocrine and paracrine interactions between tumor cells and host tissue.

Carcinoma, Renal Cell↗

Acquisition of TGF-beta 1 resistance: an important progression factor in human renal cell carcinoma.

The balance of growth regulation in tumors can be profoundly disturbed by defects in the transforming growth factor-beta 1 (TGF-beta 1) system. Thus far, investigations into the secretion of TGF-beta 1, the expression of its type I, II, and III receptors, as well as the functional intactness of the TGF-beta 1 signal transduction pathways in human renal cell carcinomas (RCC) have been lacking. The objective of the present study, therefore, was to elucidate the role of the TGF-beta 1 system in RCC. We were able to determine the status of this system in 20 primary RCC and in 30 newly established human RCC cell lines of all major histologic types. All primary RCC showed expression of TGF-beta 1 and its type I and II receptors by immunohistochemistry, irrespective of histologic type. In vitro, all RCC cell lines secreted TGF-beta 1 protein as a biologically inactive complex, which cannot interact with cell-surface receptors. Type I ALK-5-receptor mRNA and protein were detected in 29 RCC cell lines, whereas type I ALK-2-receptor mRNA was found in all cell lines. Type II-receptor mRNA and protein could be demonstrated in all cell lines analyzed, and type III-receptor mRNA was observed in five RCC cell lines. Exogenously added, biologically active TGF-beta 1 (1 ng/ml) resulted in significant (p < 0.05) inhibition of proliferation in 14 of 30 RCC cell lines. Sixteen of thirty RCC cell lines, however, proved to be TGF-beta 1-resistant. This resistance could not be explained by mutations in two "hot spot" regions of the type II-receptor gene (bp 622 to 795 and bp 1868 to 2019), as was demonstrated by DNA sequencing in the TGF-beta 1-resistant RCC cell lines. In conclusion, our observations are the first to provide evidence of an "escape" from the negative growth control of TGF-beta 1 by a significant proportion of RCC, suggesting that the acquisition of TGF-beta 1 resistance is an important progression factor for human RCC.

Biomarkers, Tumor↗

Pattern of gastric endocrine cells in microcarcinoidosis--an immunohistochemical study of 14 gastric biopsies.

A total of 14 gastric biopsy specimens from patients with microcarcinoidosis were analysed by immunohistochemical methods to evaluate the pattern of endocrine cell hyperplasia and dysplasia. All the patients had type A gastritis (autoimmune gastritis). Nonantral proliferations of gastric endocrine cells were classified according to Solcia et al. All 14 cases had hyperplasia and 13 (92.9%) of them, dysplasia of gastric endocrine cells; 9 (64.3%) of the 14 were found to have showed a coexisting invasive gastric carcinoid at the time of diagnosis of microcarcinoidosis. The patients with invasive carcinoids had higher degrees and more complex forms of endocrine dysplasia (precarcinoid lesions). The average size of the foci of the microcarcinoidosis in gastric biopsies was 0.14 +/- 0.09 cm in the patients without invasive carcinoid, as against to 0.5 +/- 0.24 cm in the group of patients with associated invasive carcinoid. Microcarcinoid gastric biopsies about 0.5 cm in size, are suggestive of adjacent invasive carcinoid. However, even frankly invasive ECL carcinoids seem to be clinically less dangerous than was thought until recently.

Adult↗

-Cardiomyopathy as the cause of death in genetic hemochromatosis-.

Hemochromatosis is an autosomal-recessive disease which causes iron-overload of various organs including liver, pancreas and heart. This report analyzes the course of hemochromatosis in two patients (a 28-year-old man and a 57-year-old woman) in whom hemochromatosis was detected because of severe cardiomyopathy. Initial symptoms were edema, anasarca and dyspnea. Further examinations showed pleural effusion, decreased left-ventricular-function, skin pigmentation, diabetes mellitus and liver cirrhosis. Although phlebotomy treatment and iron-chelation therapy with deferoxamine initially resulted in some improvement, both patients died from cardiomyopathy three months after diagnosis. The reports of these two cases underline that hemochromatosis-associated cardiomyopathy is often irreversible if severe congestive heart failure is present. In cardiac decompensation heart transplantation has to be considered as early as possible.

Adult↗

[The role of pharmacologic kidney protection in preventing post-ischemic renal failure in animal experiment].

The postischemic acute renal failure is one of the most important and frequent complications after surgery for renal artery and thoracoabdominal aortic diseases. In a canine model we studied the possible beneficial effects of Prostaglandin E1 (PGE1), Diltiazem and Superoxiddismutase (SOD) on postischemic renal function. 46 dogs were exposed to 3 hours ischemia. In 35 dogs PGE1 (n = 10), Diltiazem (n = 10), Superoxiddismutase (n = 10) or both PGE1 and SOD (n = 5) were given intravenously. 11 dogs treated with normal saline served as controls. Glomerular filtration rate, renal plasma flow, plasma creatinine, blood urea nitrogen, urine volume, free water clearance and renovascular resistance were calculated before and after renal ischemia. Radionuclide studies were performed on the third postoperative day. Two weeks later clearance measurements were repeated and kidneys were removed for histology. PGE1, Diltiazem and SOD significantly attenuated the post-ischemic fall in glomerular filtration rate and renal concentrating ability as well as the postischemic changes of tubular epithelium on histology.

Acute Kidney Injury↗

[The growth of coronary artery branches in man under physiological conditions. Morphological studies of corrosion casts of the anterior interventricular branch of the coronary artery].

In corrosion casts of the left anterior descending coronary artery and its branches of higher order, the length, diameter, and number of branches were examined in 20 hearts, from 9 adults, 3 children, 4 new-born and 4 fetuses. We counted 5245 branches in total, thereof 147 branches in the corrosion casts of adult hearts were systematically analyzed, as were 46 branches of children's hearts, 55 branches of the new-born and 35 branches of the fetuses, respectively (left anterior descending coronary arteries and branches of 1st to 6th order). The length of the left coronary arteries and of their branches of 1st and 2nd order increases to almost the same degree as the linear measurements of the hearts. The left anterior descending coronary artery is about four times as long as the 1st order branches and these have twice the length of the 2nd order branches. These differences result from the divergent course of the branches. The results indicate that no significant increase in the number of the 1st to 3rd order branches of the coronary arteries occurs from birth to adulthood in human hearts. During the postnatal growth in human hearts there seems to be no remarkable neogenesis of coronary artery branches of greater diameter. Nearly all of them exist at birth and even in the late fetal period. Their length increases harmonically with the linear measurements of the heart and they become progressively separated. These findings parallel those obtained in a previous study in pigs.

Adolescent↗

[Atypical joint symptoms as initial symptoms of varicella infection in chronic myeloid leukemia].

A 25-year-old man, known to have chronic myeloid leukaemia for four years, acutely developed a fever of 39.5 degrees and severe pain in the shoulder and hip joints. There was no evidence of joint disease. Treatment with indomethacin briefly improved the symptoms, but within 72 hours the patient developed a fulminant illness with high fever and clinical as well as biochemical signs of a severe consumption coagulopathy. Herpetiform efflorescences appeared over the head and trunk shortly before death. At autopsy there was histological and immunohistochemical evidence of a varicella infection with hepatitis, oesophageal involvement and severe internal organ bleedings. In immune-compromised patients with atypical prodromal symptoms a varicella infection must be considered so that causal treatment with acyclovir and hyperimmune-globulin can be begun in time.

Adult↗

[Capillary length in the human heart during physiological growth and under pathological conditions].

Knowledge about the capillary length in mammalian and human heart is still scanty. Because it is very difficult to examine this parameter directly we used an indirect method. The distance between the arterioles can be used as an approximately measurement for the double capillary length. We tried to measure the distances between arterioles in about 30 postmortem injected hearts using India ink to produce a kind of reflected imitated tabby (tiger) heart pattern. In addition we measured the distances between arterioles with orcein staining in histological preparation of 130 human hearts including 24 hearts with congenital vitia. Our results indicate that from birth there is a determined continuous growth of capillary length with increasing heart weight during physiological development and under pathological conditions. The capillary length in hypertrophic hearts may be an additional functional impairment of the pathological hearts.

Aging↗

[Pathologic anatomy of congenital heart defects].

The heart of neonates and infants with marked hypoplastic left- or right-heart-syndrome contains--despite the very low weight in the hypoplastic parts--myocytes of approximately the same size as in the non-hypoplastic ventricular wall. This means that the number of cells is not constant, because in contrast to the regularly developed right and left ventricular walls, the total number of myocytes in the hypoplastic parts is significantly lower. Hypertrophy of the myocardium in congenital heart disease shows histological and ultrastructural findings that are similar to those found in other forms of myocardial hypertrophy. Hypertrophy is reversible after successful surgical correction. However, regression is often incomplete, especially if surgery is delayed until adolescent or adult life. During this time scar formation in the hypertrophic ventricular wall may develop. In addition to these scars, also postoperative scar formation may contribute to the origin of arrhythmias. In hearts with cyanotic and non-cyanotic vitia distances between capillaries and capillary lengths are approximately the same as in normal hearts. Obviously, these parameters are genetically determined.

Arrhythmias, Cardiac↗

[Growth of coronary artery branches--morphometric studies of corrosion preparations of the interventricular branch of the left coronary artery in the pig and piglet].

In corrosion casts of the left anterior descending coronary artery and its branches of higher anterior order, their length, diameter, and number of branches were examined in hearts of seven mature and seven young pigs. We systematically analyzed 95 branches in the corrosion casts of the mature pig hearts and 76 branches within the corrosion casts of the young pig hearts (left anterior descending coronary arteries and branches of 1st-5th order). The lengths of the branches of 1st order and the diameters of the branches of 1st and 2nd order had increased to the same degree as the lengths and diameters of the main trunk of the left anterior descending coronary artery and the linear measurements of the hearts. In the area of the more peripherally located branches, the differences showed a tendency to decrease. The number of branches differed only slightly between mature pigs' and young pigs' corrosion casts. These results show that during physiologic growth, no or only unremarkable new development of coronary artery branches occurs.

Animals↗

[The combination of atrial myxoma and multiple skin myxomas: a characteristic symptom complex?].

In 1980, a then 7-year-old boy from Yugoslavia had an atrial myxoma removed. Since then there have been no abnormal cardiac signs or symptoms. Between 1982 and 1986 five cutaneous myxomas in the trunk region were removed. None of the tumours had histological signs of malignancy. These observations can be fitted into the symptom complex (described in 1985 by Carney et al.) of cardiac myxoma, cutaneous myxoma, changes in skin pigmentation, and abnormal endocrine functions--although not all signs need be present together. A disposition towards the development of myxomatous tumours is to be assumed in these patients. One should, therefore, always suspect an occult cardiac myxoma in the presence of multiple cutaneous myxomas. Appropriate diagnostic measures need to be taken before the typical and sometimes lethal consequences of a cardiac myxoma have occurred.

Child↗

Evidence for muscle fiber hyperplasia in the septum of patients with hypertrophic obstructive cardiomyopathy (HOCM). Quantitative examination of endomyocardial biopsies (EMCB) and myectomy specimens.

Asymmetric thickening of the septum is one of the hallmarks of hypertrophic obstructive cardiomyopathy (HOCM). Endomyocardial biopsies (EMCB) from the right side of the septum and myectomy specimens from its left part were morphometrically investigated to determine the size of septal myocytes, as well as the volume density of the interstitium and fibrous tissue, and to estimate the number of transseptal muscle fiber layers. EMCBs of seven patients with normally shaped hearts, taken as controls (N), EMCBs of seven consecutively examined patients with HOCM (HOCM 1), and of seven HOCM patients with additionally available myectomy specimens (HOCM 2) were evaluated. In myectomy specimens muscle fiber thickness and volume density of the interstitium and fibrous tissue were significantly increased, as compared with the findings in the EMCBs. The echocardiographically determined septal thickness was increased by 93% in HOCM 1 and by 150% in HOCM 2 compared with controls; however, the increase in muscle fiber thickness and volume density of the interstitium did not give a sufficient explanation for the increased septal thickness in both groups of HOCM. Based on EMCB data, the estimated number of septal muscle fiber layers was 715 +/- 93 in group N, 1242 +/- 149 in HOCM 1, and 1119 +/- 177 in HOCM 2, while 810 +/- 232 layers were estimated according to the findings from myectomy specimens. Taking into account that EMBC represent only 1 mm of septal thickness, and myectomy specimens up to 15 mm, an increase in the septal muscle cell layers of about 30% can be estimated in HOCM hearts.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗

A novel human malignant fibrous histiocytoma cell line of the heart (MFH-H) with secretion of hematopoietic growth factors.

Primary malignant fibrous histiocytoma (MFH) exhibits an extremely adverse prognosis. Investigations into the principles determining the biological aggressiveness of this cardiac tumor would be facilitated by an appropriate in vitro model. Therefore, we report on the first permanent cell line (MFH-H), derived from a human cardiac MFH. The original tumor had shown coexpression of cytoskeletal filaments typical of mesenchymal (vimentin), epithelial (cytokeratins) and neurogenic (neurofilaments) differentiation. This potential for multidirectional differentiation was observed in the MFH-H cell line as well and indicated marked plasticity of gene activation acquired during the process of neoplastic transformation. Pronounced genetic alterations also became evident from cytogenetic analysis, which revealed a highly variant karyotype with multiple numeric and structural chromosomal aberrations. Secretion of G-CSF, GM-CSF and M-CSF was shown to be another feature of deregulated gene expression in MFH-H cells. Direct autocrine effects of their hematopoietic growth factors, however, were precluded by the lack of the corresponding receptors. In conclusion, the cell line MFH-H will provide an appropriate in vitro model to analyze the biological properties of this cardiac malignancy in more detail, especially with regard to a possible immunomodulating capacity of MFH-derived hematopoietic growth factors.

Adult↗