Biomedical subjects

T Ekfors

Publications and source records attributed to T Ekfors.

At least 19 recordsLinked to original sources

PubMed2001

Decorin is produced by capillary endothelial cells in inflammation-associated angiogenesis.

Decorin is a small extracellular chondroitin/dermatan sulfate proteoglycan that has previously been shown to be involved in the angiogenesis-like behavior of endothelial cells (ECs) in vitro. There is also evidence that decorin plays a role in angiogenesis in vivo. In this study we sought to further explore the involvement of decorin in angiogenesis in vivo, especially in that associated with inflammation. We found by CD31 immunostaining of ECs that in giant cell arteritis there are capillary blood vessels not only in the adventitia as in uninvolved temporal artery wall, but also in the media and the external zone of the thickened intima. Localization of decorin by antiserum LF-30 in adjacent sections showed that in normal temporal artery wall decorin resides mainly in the media and the adventitia, whereas in inflamed temporal artery wall decorin is distributed throughout the vessel wall including the intima. Furthermore, the most intense reaction for decorin was evident in ECs of capillary neovessels within the media and the thickened intima of inflamed temporal artery wall. Decorin was also found in capillary ECs in certain pathological and physiological conditions in which the pivotal role of angiogenesis is more generally accepted. Pyogenic granulomas, granulation tissue of healing dermal wounds, and ovaries at different phases of follicle and corpus luteum formation all contained widely distributed CD31-positive capillaries. Decorin, on the other hand, was found in capillary ECs in pyogenic granulomas and granulation tissue, but not in those in the ovaries. The assessment of the degree of inflammation in the specimens with the presence of CD68-positive macrophages showed that the pyogenic granuloma, granulation tissue, and giant cell arteritis specimens were rich in macrophages around the decorin-positive capillaries. In contrast, the ovarian specimens were populated with fewer macrophages and even they were not located in close vicinity of capillaries negative for decorin. Our results confirm that decorin is involved in angiogenesis in vivo and, particularly, in conditions in which the inflammatory component is dominant.

Adult↗

PubMed2001

Cysteine proteinases in chondrosarcomas.

The aim of the present study was to define the role of cathepsins B, H, K, L and S in the pathogenesis of human chondrosarcomas. For this purpose 40 tumour samples obtained from 12 patients with the diagnosis of conventional chondrosarcoma were systematically investigated for the expression of cathepsin mRNAs by Northern hybridisation, and for immunohistochemical localisation of the proteins. Northern analysis demonstrated the highest levels of cathepsins B and L in a recurring grade 1 chondrosarcoma, and in a grade 3 chondrosarcoma and in fibrous histiocytomas. Increased expression of cathepsin K mRNA was seen in seven chondrosarcomas, as well as in control tumours; fibrous histiocytomas, osteosarcomas, enchondromas and a giant cell tumour of bone. Cathepsin L was immunolocalised within the large chondrocytes, while cathepsin K was predominantly localised in large multinucleated osteoclastic cells and in some hypertrophic chondrocytes. These results suggest that chondrosarcoma can be included in the growing list of tumours, where cathepsins may well be involved in tumour progression. The simultaneous upregulation of cathepsins B and L, together with matrix metalloproteinase-13, and the association of cathepsin K with negative prognostic parameters suggests that an aggressive biological behaviour of chondrosarcoma may be related to the synthesis of cysteine proteinases and activation of other proteolytic enzymes. If this turns out to be the case, cathepsin inhibitors could provide the much needed adjuvant therapy for chondrosarcomas.

Adult↗

PubMed2001

Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human chondrosarcomas.

The aim of the present study was to characterise the ability of malignant chondrosarcomas to invade normal bone by analysing their production of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). For this purpose 12 chondrosarcomas were investigated for the expression of mRNAs for several MMPs and all 4 TIMPs by Northern hybridisation, and for immunohistochemical localisation of the proteins. A characteristic finding of these analyses was increased expression of MMP-13, MMP-14 and TIMP-2 mRNAs in chondrosarcomas when compared with nonmalignant control samples. Individual chondrosarcomas also exhibited elevated levels of MMP-1, MMP-7 and MMP-9 mRNAs. The results of Northern hybridisations were supported by immunohistochemical stainings of the corresponding tumour areas for MMP-2, MMP-14 and TIMP-2, further suggesting that these may have prognostic value for determining whether individual chondrosarcomas are locally aggressive or have a probability of recurrence. Another finding of the present study was a marked heterogeneity in histologic appearance and gene expression of the chondrosarcomas, emphasising the importance of analysing several areas of these tumours to get representative results. These findings suggest that analysis of MMPs could be a useful diagnostic indicator in patients with cartilaginous tumours and could help in differentiating between a low-grade malignant chondrosarcoma and a benign growing enchondroma.

Adolescent↗

PubMed2001

Leiomyoma of the urinary bladder.

We report a case of rare benign bladder leiomyoma. The patient was a 42-year old man complaining impotence. Digital rectal examination revealed a palpable pelvic tumor. Transurethral ultrasonography, computed tomography (CT), and magnetic resonance image (MRI) examinations all showed a cystic tumor measuring 10 x 8 cm. On the basis of these findings leiomyoma was suspected already before operation. The tumor was removed by open resection of bladder, and the diagnosis was confirmed by histology and positive immunohistochemistry.

Adult↗

PubMed2001

Leiomyoma of the urinary bladder.

Adult↗

PubMed2000

Adenocarcinoma of the pancreas metastatic to the mandible.

Explore the source record for details and available documents.

Adenocarcinoma↗

PubMed1999

Clinical correlations of genetic changes by comparative genomic hybridization in Ewing sarcoma and related tumors.

Our previous comparative genomic hybridization (CGH) study of Ewing sarcoma and related tumors showed that DNA sequence copy number increases of 1q21-q22 and of chromosomes 8 and 12 were associated with trends toward poor survival (Armengol et al., Br J Cancer 1997, 75, 1403-1409). These trends were not statistically significant. In the present study, we analyzed 28 primary Ewing sarcomas and related tumors by CGH to study whether these (or other) changes have prognostic value in these tumors. Twenty-one tumors (75%) had changes with a mean of 1.9 changes per tumor. The most frequent aberration was gain of chromosome 8 in 10 tumors (36%). Five tumors (18%) had copy number increases at 1q21-22 and 5 had gain of 7q. Copy number increase of 6p21.1-pter, gain of chromosome 12, and loss of 16q were seen in 11%. Copy number increases of 1q21-q22 and of chromosomes 8 and 12 were associated with trends toward worse outcome, but the differences did not reach statistical significance. A novel finding is the association of copy number increase at 6p with worse distant disease-free (P = 0.04) and overall survival (P = 0.004). To confirm this finding and to see whether copy number increases of 1q21-q22 and of chromosomes 8 and 12 have definite prognostic value, a larger number of cases needs to be studied.

Adolescent↗

PubMed1999

Effects of hexose sugars: glucose, fructose, galactose and mannose on wound healing in the rat.

The effects of four hexose sugars (D-glucose, D-fructose, D-galactose, D-mannose) on the developing granulation tissue in rats were examined. Cylindrical hollow sponge implants were used as an inductive matrix for the growth of granulation tissue. In the test group, the implants were injected with 0.1 ml of solution containing the different hexoses in 0.01, 0.1 and 1 M concentrations daily for 7 days while the implants of the control groups were injected with 0.1 ml of phosphate-buffered saline solution only. Analyses of granulation tissue and wound fluid in the sponge implants were carried out 7 days after implantation. The results demonstrated that galactose caused a significant increase in the accumulation of granulation tissue as estimated by histological analyses, but no significant differences were observed in various chemical analyses. In striking contrast, statistically significant decreases were observed in the number of leukocytes in wound fluid, in the amount of DNA, RNA, collagen hydroxyproline, nitrogen, hexosamines and uronic acids in sponges treated with 0.1 or 1 M mannose, reflecting decreased granulation tissue formation. This effect was also observed in histological analyses of the specimens. There were no major changes in sponges treated with glucose or fructose. In summary, the findings of the present study demonstrate that galactose may enhance wound healing and mannose treatment inhibits the inflammatory reaction in wound healing and decreases granulation tissue formation in an experimental wound model.

Animals↗

PubMed1998

Expression of group II phospholipase A2 in Paneth cells of an adenoma of the rectum. A case report.

A case of tubulovillous adenoma in the rectum of a 51-year-old man is presented. The tumour contained numerous Paneth cells which formed well-developed glands in the basal areas. Group II phospholipase A2 and lysozyme were found in the tumour cells by immunohistochemistry. mRNA of group II phospholipase A2 was localized in the tumour cells by in situ hybridization. It was concluded that a considerable part of this rare type of tumour consisted of Paneth cells which were capable of synthesizing group II phospholipase A2.

Adenoma, Villous↗

PubMed1998

Immune responses and clinical outcome of massive human osteoarticular allografts.

Cell mediated immune responses as measured by lymphocyte proliferation induced by the mitogens phytohemagglutinin and concanavalin A and antigen extracts of donor derived bone were studied within 2 years after wide resection of bone tumors in 18 patients receiving fresh frozen massive osteoarticular allografts. No uniform changes were seen in mitogen induced responses in 18 patients. However, five of nine patients tested with antigen extracts of donor derived bone showed elevated immune responses, one moderate and four weak. The incorporation of the allograft (evaluated by repeated radiographs; specific isotope techniques; clinical outcome assessed by the functional rating scores of Mankin-Waber and the Musculoskeletal Tumor Society; and histologic biopsy findings on new bone formation) did not differ in these patients from those in patients without any response to donor derived tissue. During a long term followup (mean, 11 years; range, 2-20 years), degenerative joint and sclerotic density bone changes developed after 2 to 4 years without correlation to immune responses. Histologic specimens showed no signs of immunologic reaction, and no clinical rejection episodes were recorded. A slightly variable immune response to allograft bone seems to occur, but its clinical significance for outcome of the grafts remains to be determined. The low immune responses might reflect a low antigen release rate through an indirect pathway or immunologic tolerance to antigens or proteins shed from massive allografts that are nonliving scaffold implants during the creeping substitution process, corresponding to the low immune response and the slow histologic repair.

Adolescent↗

PubMed1997

Loss of expression of the p16INK4/CDKN2 gene in cutaneous malignant melanoma correlates with tumor cell proliferation and invasive stage.

The G1/S checkpoint of the cell cycle is regulated by p16, p53 and RB tumor suppressor genes. Loss of expression of the p16INK4 tumor suppressor protein, the product of the CDKN2 gene, has been associated with a wide variety of human malignancies. Mutations, loss of heterozygosity and deletions of the CDKN2 locus have been reported in sporadic and familial cutaneous malignant melanomas (CMM). To investigate the role of the alterations of p16 expression in melanoma, we evaluated by immunohistochemistry the p16 expression and cell proliferation in 79 primary CMM and 10 benign melanocytic nevi (BMN). Forty-six melanomas (58%) and all BMN were found to be p16 positive; 33 melanomas (42%) were considered p16 negative. The extent of invasion according to Clark was significantly higher in p16-negative tumors than in p16-positive tumors. Cell proliferation as expressed by the proportion of positive cells in Ki-67 immunostaining was found to be significantly higher in p16-negative tumors than in p16-positive tumors, although there was no significant difference in the mitotic index between p16-positive and p16-negative tumors. In p16-positive tumors, the number of Ki-67-positive cells correlated with the mitotic index; in p16-negative tumors, there was no correlation between these parameters. Our data suggest that loss of p16 expression is more common in advanced melanomas, and that G1/S checkpoint regulation is disrupted in p16-negative melanomas. Our results show that loss of p16 expression is a common event in primary melanomas, which further substantiates the role of p16 as a major tumor suppressor.

Adult↗

PubMed1997

Treatment results of osteogenic sarcoma. An evaluation of 36 patients treated during 30-year period in south-western Finland.

Histological re-evaluation revealed 36 osteogenic sarcoma (OS) patients for analysis in South-Western Finland treated between 1958 and 1987. In 21 cases (58%) the tumour was located in the knee region. The mean age at diagnosis was 28 years (range: 5-62 years) and the follow-up time of the patients was at least 5 years or until death. In 29 patients without metastases at the time of diagnosis, the extent of the primary tumour was T2 in 37% and T3 in 63% of the patients. There were no differences regarding the extent of the primary tumour, delay of the diagnosis, mean age of the patients, or duration of the symptoms while comparing the three decades of the study. Before the 1970s the treatment consisted of surgery with or without radiotherapy in most cases. Since the 1970s the combination of surgical treatment (amputation or wide excision) and adjuvant chemotherapy was the most common treatment modality. Since the late 1970s limb-salvage surgery has been applied in selected cases, and it seems to be justified. None of the patients treated before 1970 survived for 5 years. The 5- and 10-year survival of all 36 patients was 44.4% and 33.6%, respectively. In non-metastatic patients both the 5- and 10-year disease-free survival was 46.7%. A certain group exhibiting a good prognosis was found; the 10-year survival of the 10 patients with OS in extremities, treated with combined chemotherapy and surgery, was 70%. The median survival time was significantly longer for the patients with an intracompartmental tumour extent of T2 (112 months) compared with an extracompartmental extent of T3 (23 months), and for the patients with the primary tumour in the knee region (112 months) compared with other locations (18 months). The long-term survival of the OS patients has improved concomitantly with the multimodality of the treatment.

Adolescent↗

PubMed1996

Immunohistochemical expression of p53 protein, mitotic index and nuclear morphometry in primary malignant melanoma of the skin.

The immunohistochemical expression of the p53 tumor suppressor protein and the nuclear morphometric parameters were studied in 80 primary skin melanomas. The mitotic index was counted in 64 tumors. In 95% of the tumors p53 positive nuclei were detected, but in only 31% of the cases was the proportion of positive nuclei 3% or higher. The mitotic indices and the mean nuclear areas were not significantly different in melanomas with different p53 expression levels. The p53 positive nuclei had a larger mean nuclear area than the p53 negative nuclei. p53 expression did not increase with melanoma thickness. In Cox's stepwise proportional hazards model, the ratio of mean nuclear long and short axis and melanoma thickness had independent prognostic value, while the level of p53 expression, the mitotic index, and the mean nuclear area were not significantly associated with survival. We conclude that the nuclei expressing p53 protein are larger than p53 negative nuclei. The level of immunohistochemical expression of p53 is low in primary skin melanoma, and it is not valuable as a general prognostic marker for this tumor. p53 expression is not associated with melanoma thickness, indicating that high p53 expression is not a late phenomenon in the progression of this tumor.

Adolescent↗

PubMed1996

MR imaging in the presence of small circular metallic implants. Assessment of thermal injuries.

PURPOSE: The thermal effects of MR imaging in the presence of circular nonferro-magnetic metallic implants were studied in 6 rabbits. MATERIAL AND METHODS: A sternotomy was performed and fixed with stainless steel wires, and small titanium rings (diameter 3 mm) were placed on the surface of the ascending aorta and subcutaneous tissue of the thigh. Four of the rabbits were exposed to an imaging procedure with a 1.5 T scanner applying a T1-weighted spin-echo sequence and a gradient echo sequence. Two of the animals served as unexposed controls. Thirty-six hours after the exposure, tissues adjacent to the implants were examined histologically and compared with corresponding samples of the control animals. RESULTS: In the area of the titanium rings, histologic analysis revealed slight inflammatory changes apparently caused by the operation. No evidence of thermal injury was found, suggesting that the presence of the rings does not contraindicate MR examinations. Necrosis was noted in all of the sternal specimens. This was probably post-operative, but it impaired the assessment of thermal injury in this area.

Animals↗

PubMed1994

Expression of inhibin alpha, beta A and beta B messenger ribonucleic acids in the normal human ovary and in polycystic ovarian syndrome.

We studied the cellular distribution of inhibin alpha, beta A and beta B mRNAs in the normal human ovary and in polycystic ovarian syndrome (PCOS) by in situ hybridization. Our results show that human granulosa cells express inhibin alpha, beta A and beta B subunit mRNAs, and theca cells express inhibin alpha and beta A subunit mRNAs. The co-localization of alpha and beta A mRNAs in theca cells supports the hypothesis that inhibin also has an autocrine function in these cells. We did not detect any inhibin subunit mRNA in the granulosa cells of atretic follicles, while theca cells also expressed alpha subunit mRNA in those follicles. The present findings suggest that the expression of inhibin subunits is regulated differently in human follicular granulosa and theca cells. It has been speculated that inhibin may be involved in the development of PCOS. Our results show that the cellular localization of inhibin subunit mRNAs is not disturbed in PCOS ovaries.

Female↗

PubMed1994

Incorporation and clinical results of large allografts of the extremities and pelvis.

The results of implantation of 37 large deep-frozen allografts with 29 osteoarticular grafts of the extremities and pelvis following the resection of malignant or aggressive benign bone tumors were evaluated at followup (mean, 6 years; range, 2.5-20 years). The patients had excellent or good results in 62% of all cases according to the Mankin-Waber functional rating score, and a corresponding rating of 81% in the Musculoskeletal Tumor Society Score. Benign versus malignant disease rated 83% and 76%, respectively, in the Musculoskeletal Tumor Society Score, and 67% and 46%, respectively, in the Mankin-Waber score. Radiological and nuclear medicine (single-photon emission computed tomography) studies and histological biopsies indicated that the incorporation, perfusion, and replacement with new bone was only partial and of a low degree. Late degenerative cartilage and sclerotic changes occurred in 20 of 29 cases with osteoarticular grafts. The best functional results were achieved with knee osteoarticular allografts (81%-88%) compared with modest results in the proximal humerus (69%) and hemipelvis (57%) according to the Musculoskeletal Tumor Society Score rating. Chemotherapy did not influence the union or infection rate of the allografts. In the 4 cases (11%) with infection, all grafts could be salvaged, but the functional results were only 63% in the Musculoskeletal Tumor Society Score. The overall complication rate was high (57%); graft-related complications occurred in 43%, including fatigue fractures in 27%. There were no cases of nonunion at the host graft junction. Clinical rejection did not occur. These clinical results may be improved in the future by new technology that uses bone substitutes, growth factors, and bone morphogenetic proteins.

Adult↗

PubMed1993

Pathogenesis of primary central nervous system lymphoma: invasion of malignant lymphoid cells into and within the brain parenchyme.

The pattern of invasion of lymphoid cells to the central nervous system (CNS) was analyzed for malignant lymphocytes in 19 primary CNS lymphomas (PCNSL) and six intracerebral metastatic lymphomas, and for reactive lymphocytes in four encephalitides and three astrocytomas. The identical spreading pattern in both primary and metastatic lymphomas suggests that even in the so-called primary CNSL the malignant transformation has occurred outside the CNS. The compact perivascular cuffs of both malignant and reactive lymphocytes were never seen around the smallest capillaries, and they were most common around vessels larger than 15 microns in diameter. Perivascular lymphocytes resided within the reticulin network, which was immunopositive for collagen type III and IV, laminin and fibronectin. These findings imply that lymphocytes extravasate at the level of arterioles and venules and spread along the enlarged perivascular space. When the outer boundary of the perivascular network was broken, malignant lymphocytes spread diffusely into the CNS parenchyme; a pattern which is different from that of other CNS metastases. The widespread immunopositivity for the homing cell adhesion molecule CD44 in the CNS vessels and parenchyme, especially in the white matter which is the predilection site of PCNSL, suggest that this adhesion molecule and its ligands participate in spreading of malignant lymphocytes within the CNS parenchyme.

Adult↗

PubMed1993

What happens to the Valtrac anastomosis of the colon? A follow-up study.

Late results after colonic anastomoses performed with the biofragmentable anastomosis ring (BAR; Valtrac; Davis & Geck, Wayne, NJ) were evaluated in 30 patients who had undergone a left-sided colonic or rectosigmoid anastomosis a mean of 24.5 (range, 12-38) months earlier. Patients were asked about their late postoperative recovery and their bowel habits. A barium enema was performed, and then a flexible endoscopy was done, during which the anastomotic area was evaluated both in macroscopic terms and histologically. One of the patients had died, and three refused to participate in the investigation. Of the remaining 26 patients, one had been reoperated on 22 months after the primary sigmoid resection. The reason for reoperation was an anastomotic stricture. One of the patients was admitted to the hospital during the study and was operated on for reasons not related to the anastomosis. Twenty-four patients underwent the study scheme. All had recovered uneventfully. Sixteen anastomoses could not be identified radiologically and seven not even during endoscopy. Histologically, there was mild-to-moderate fibrosis and scarring in 17 anastomoses, and, in the seven that could not be identified, only normal colonic mucosa was found. The late results of BAR anastomoses are satisfying, and the rate of complications is acceptable.

Adult↗