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H Helin

Publications and source records attributed to H Helin.

At least 19 recordsLinked to original sources
PubMed2006

Thomsen-Friedenreich oncofetal antigen in Schistosoma mansoni : localization and immunogenicity in experimental mouse infection.

Our preliminary observation, that sera from schistosomiasis patients react with carcinomas, raised the possibility of antigenic cross-reactivity. We here extend this observation to show that mice experimentally infected with Schistosoma mansoni react with human urothelial and transitional bladder carcinomas and also with a gastric carcinoma cell line, AGS. To identify cross-reacting epitopes, we looked for the expression of carcinoma markers in schistosome worms and eggs using monoclonal antibodies against tumour antigens MUC1, Tn and TF (also known as the oncofetal Thomsen-Friedenreich antigen or T antigen). Immunohistochemical staining showed that the TF-epitope is present in adult intravascular S. mansoni worms and eggs deposited in tissues of infected animals. The localization of TF-immuno-reactive material in schistosomes was seen at the parasite surface between male and female worms and around trapped eggs in the liver. This localization is consistent with the antigen being secreted. Mice experimentally infected with S. mansoni, developed circulating antibodies against the TF-epitope (identified as Gal(beta1-3) GalNAc-O-R) as seen in ELISA using TF-expressing asialoglycophorin (AGP) as antigen. The observed anti-TF response in S. mansoni-infected mice reflects the complexity of host-parasite interactions in this infection.

Animals↗
PubMed2006

Amplification of the epidermal growth factor receptor in astrocytic tumours by chromogenic in situ hybridization: association with clinicopathological features and patient survival.

Chromogenic in situ hybridization (CISH) was used to detect amplification of the epidermal growth factor receptor (EGFR) gene in tissue microarrays of tumours derived from 287 patients with grade II-IV diffuse astrocytomas. Amplification was found in 32% of the tumours with a highly significant association with histological grade (4% in grade II, 21% in grade III and 39% in grade IV; P < 0.001). Amplification of the EGFR gene was more common in primary than in secondary glioblastomas (41%vs. 16%, P = 0.033). Overexpression of EGFR mRNA and protein (wild-type and vIII variant) was found to correlate with EGFR gene amplification (P = 0.028, P = 0.035 and P = 0.014 respectively), but wild-type EGFR protein was also frequently overexpressed in tumours without EGFR gene amplification. Patients with older age (P < 0.001) and tumours with lack of p53 overexpression (P = 0.03) and higher apoptosis rate (P < 0.001) had significantly more EGFR gene amplifications than their counterparts. No such correlation with apoptosis was found in glioblastomas. The survival of patients with EGFR gene-amplified grade III tumours was significantly shorter than in those with grade III non-amplified tumours (P = 0.03). No such difference was noted in glioblastomas (grade IV tumours). Our data verify the central role of EGFR in the pathobiology of astrocytic tumours, and highlight the advantages of CISH as a simple and practical assay to screen for EGFR gene amplification in astrocytic tumours.

Adolescent↗
PubMed2006

Oxidative/nitrosative stress and peroxiredoxin 2 are associated with grade and prognosis of human renal carcinoma.

Peroxiredoxins (Prxs) 1-6 were assessed in 138 renal cell carcinomas (RCC) using immunohistochemistry and selected samples by Western blotting analysis. Oxidative/nitrosative damage was evaluated using nitrotyrosine immunoreactivity. The expressions of Prxs were correlated with tumor grade and survival and nitrotyrosine reactivity. Non-malignant kidney tubular cells showed positivity with variable intensity for all six Prxs. In RCCs, most cases were positive for Prxs 1 and 2, while only 15-20% of tumors showed expression for Prxs 3 and 4. Prx 2 was associated with tumors of a lower grade (p=0.009) and with a lower frequency of distant metastases (p=0.046). Patients with tumors expressing Prx2 had better prognosis (p=0.027). Instead, nitrotyrosine was significantly associated with high grade tumors (p=0.001). Compared with the non-malignant kidney tubular cells, low Prx expression in the tumor cells can make them more susceptible to oxidative damage. Prx 2 was more abundantly expressed in low grade tumors, suggesting that this protein could play a role in preventing the development of oxidative damage, which in turn can lead to the activation of pathways leading to aggressive tumors.

Adult↗
PubMed2006

Antioxidant enzymes in renal cell carcinoma.

The aim of the study was to estimate the significance of oxidative/nitrosative damage and expression of antioxidant enzymes in renal cell carcinomas (RCC). For this we investigated immunohistochemically six antioxidant enzymes (AOEs) including MnSOD, ECSOD, thioredoxin, thioredoxin reductase, and gammaglutamyl cysteine synthetase heavy and light chain in 138 RCCs. As an indicator of oxidative/nitrosative damage, sections were stained with an antibody to nitrotyrosine. The extent of apoptosis was evaluated by TUNEL method and proliferation by immunohistochemistry to Ki67. Variable expression of all AOEs could be seen in RCC with expression of MnSOD being strongest. Nitrotyrosine was significantly associated with high grade tumors. MnSOD was associated with tumors of a lower stage. Cases showing ECSOD reactivity had higher and cases expressing thioredoxin lower apoptotic index than other tumors. No association with patient prognosis was observed. According to the results renal cell carcinomas show oxidative/nitrosative damage which, according to nitrotyrosine staining, was higher in high grade tumors. Of AOEs, MnSOD was more abundantly expressed in low stage tumors suggesting that its antioxidant function could play a main role to prevent development of oxidative damage leading to more aggressive tumors.

Adult↗
PubMed2005

Claudins 1, 3, 4 and 5 in gastric carcinoma, loss of claudin expression associates with the diffuse subtype.

In this study expression of claudins 1, 3, 4 and 5 were studied in 118 cases of gastric carcinoma and compared with proliferation, apoptosis and E-cadherin expression. Expression of all these claudins could be seen in gastric carcinoma, most prominently for claudin 4, and least expression was found for claudin 5. All claudins showed significantly more expression in gastric carcinomas of intestinal type. Their expression was significantly associated with each other. Expression of claudins 4 and 5 was associated with E-cadherin. Strong expression of claudin 5 was associated with higher cell proliferation and apoptosis. Claudin 3 expression had an association with a better prognosis of the patients, especially in the intestinal type. The results show that expression of claudins 1, 3, 4 and 5 is lower in diffuse-type gastric carcinomas. Possibly they play a role in determining the diffuse phenotype and loose cohesion of cells in diffuse type of gastric carcinoma in a similar manner as E-cadherin. The loss of their expression does not clearly associate with poorer prognosis of the patients, except for claudin 3, where strong expression was associated with a better outcome of the patients, a feature especially related to intestinal-type tumours.

Adenocarcinoma↗
PubMed2005

Amplification of HER-2 in gastric carcinoma: association with Topoisomerase IIalpha gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab.

BACKGROUND: HER-2/neu gene amplification has predictive value in breast cancer patients responding to trastuzumab. We wanted to investigate the frequency and clinical significance of HER-2/neu amplification in gastric carcinoma. PATIENTS AND METHODS: The frequency of HER-2/neu and Topoisomerase IIalpha gene amplification was studied in adenocarcinomas of the stomach (n=131) and the gastroesophageal junction (n=100) by chromogenic in situ hybridization (CISH). Sensitivity of a gastric cancer cell line N87 with HER-2/neu amplification to trastuzumab was studied by a cell viability assay and compared with that of a HER-2 amplified breast cancer cell line SKBR-3. Growth inhibition of N87 cells was also verified in vivo in N87 xenograft tumors. RESULTS: HER-2/neu amplification was present in 16 (12.2%) of the 131 gastric and in 24 (24.0%) of the 100 gastroesophageal adenocarcinomas. Co-amplification of Topoisomerase IIalpha was present in the majority of gastric (63%) and esophagogastric junction cancers (68%) with HER-2/neu amplification. HER-2/neu amplification was more common in the intestinal histologic type of gastric cancer (21.5%) than in the diffuse (2%) or the mixed/anaplastic type (5%, P=0.0051), but it was not associated with gender, age at diagnosis or clinical stage. Presence of HER-2/neu amplification was associated with poor carcinoma-specific survival (P=0.0089). HER-2/neu targeting antibody trastuzumab inhibited the growth of a p185(HER-2/neu) overexpressing gastric and breast carcinoma cell lines (N87 and SKBR-3) with equal efficacy. CONCLUSIONS: HER-2/neu amplification is common in the intestinal type of gastric carcinoma, and it is associated with a poor outcome. HER-2 might be a useful target in this disease, and this hypothesis deserves to be investigated in clinical trials.

Adenocarcinoma↗
PubMed2005

Mechanisms dependent on tryptophan catabolism regulate immune responses in primary Sjögren's syndrome.

To investigate the possible role of tryptophan metabolism in immune regulation of primary Sjögren's syndrome (pSS) the serum concentrations of tryptophan and its metabolite kynurenine were measured by reverse-phase high-performance liquid chromatography (HPLC) in 103 patients with pSS, 56 patients with sicca symptoms and 309 healthy blood donors. The kynurenine per tryptophan ratio (kyn/trp), which reflects the activity of the indoleamine-pyrrole 2,3-dioxygenase (IDO) enzyme involved in tryptophan catabolism, was calculated. Both female and male patients with pSS had significantly higher serum kynurenine concentrations and kyn/trp than subjects with sicca symptoms or healthy blood donors. The median (quartile range) concentration of kynurenine in female patients with pSS was 2.41 micromol/l (1.86-3.26) compared with 1.85 micromol/l (1.58-2.38, P < 0.0001) in subjects with sicca symptoms and 1.96 micromol/l (1.65-2.27, P < 0.0001) in healthy blood donors. Their kyn/trp x 1000 was 34.0 (25.1-44.3) compared with 25.3 (21.1-31.5, P < 0.0001) in subjects with sicca symptoms and 24.3 (21.0-28.9, P < 0.0001) in healthy blood donors. Female pSS patients with high IDO activity (kyn/trp x 1000 > or = 34.0) had significantly higher ESR, serum C-reactive protein, serum IgA and serum beta-2 microglobulin concentrations as well as higher serum creatinine levels, and they had positive antinuclear antibodies more frequently and presented with more American-European consensus group criteria than those with low IDO activity (kyn/trp x 1000 < 34.0). These data suggest that mechanisms dependent on tryptophan catabolism regulate immune responses in pSS. Tryptophan degradation is enhanced in patients with pSS, and high IDO activity is associated with severity of pSS.

Antibodies, Antinuclear↗
PubMed2004

Cockroach allergen extract stimulates protease-activated receptor-2 (PAR-2) expressed in mouse lung fibroblast.

OBJECTIVE: To investigate whether cockroach allergen extract can stimulate Protease-activated receptor 2 (PAR-2) expressed in mouse lung fibroblast. MATERIALS: We established an immortalized lung fibroblast cell line, DM5, from PAR-2 deficient mice. By stable transfection with either an empty vector (DM5/EV) or an expression vector encoding mouse PAR-2 cDNA (DM5/Par2), a pair of lung fibroblast cell lines with or without functional PAR-2 expression were prepared. TREATMENT: The cells were exposed to cockroach allergen extract [up to 800 protein nitrogen unit (PNU)/ml], trypsin (up to 100 nM), SLIGRL agonist peptide (up to 500 microM), and trans-cinnamoyl-LIGRO agonist peptide (up to 400 microM). METHODS: The cells were loaded with Fluo-3 calcium indicator and mobilization of intracellular calcium with the stimuli was monitored by a fluorometric plate reader. Extracellular signal-regulated kinase (ERK) phosphorylation was examined by Western blot analysis using an anti-phospho ERK antibody. RESULTS: The cockroach extract induced intracellular calcium transients in a concentration dependent manner in DM5/Par2 but not in DM5/EV. The activity was abolished when the cockroach extract was heat denatured or pre-incubated with PMSF (phenylmethanesulfonyl fluoride) prior to the assay. Concomitantly, ERK phosphorylation was seen in DM5/Par2 with the cockroach extract but not with a heat-denatured extract. The responses were sensitive to an inositol-1,4,5 triphosphate antagonist (2-APB) indicating that calcium was mobilized from intracellular store. CONCLUSIONS: Cockroach allergen extract can activate PAR-2 and thereby stimulate mouse lung fibroblasts likely through protease(s). The present study proposes a potential mechanism for cockroach antigens, similar to house dust mite antigens, in the etiology of respiratory diseases.

Allergens↗
PubMed2004

Chromosomal gains and losses detected by comparative genomic hybridization and proliferation activity in renal cell carcinoma.

OBJECTIVE: The number of DNA losses found using comparative genomic hybridization (CGH) and the proliferation index MIB-1 have been shown to be prognostic factors in renal cell carcinoma (RCC). We evaluated the associations of these two factors with each other and with histopathology and clinical outcome. MATERIAL AND METHODS: In this prospective study, specimens from 20 primary RCCs were investigated using CGH and MIB-1 assay. The associations of the commonest chromosomal aberrations with histopathology, stage and the clinical outcome of the disease were evaluated. RESULTS: CGH detected genetic aberrations in all tumours. Losses of genetic material (85%) were more common than gains (65%). Most common was loss in the short arm of chromosome 3, which was found in 70% of the tumours. Other frequent changes (20%) were losses of 4q, 13q, 18 and Xp, as well as gains of 5q, 7p, 7q (25%) and chromosome 12. The number of deleted chromosomal areas varied from none to six. The MIB-1 index varied from 0 to 39 (median 4.0). The total number of chromosomal aberrations or deletions showed no association with MIB-1 index or nuclear grade. Most grade 1 and 2 tumours showed a low MIB-1 index. All nuclear grade 4 tumours progressed and were associated with short survival. CONCLUSION: CGH gives an overview of DNA changes in RCC and helps to locate targets for more precise genetic evaluation. CGH findings are also helpful for classifying tumours. In this study, genetic aberrations in primary RCCs were not associated with histopathology, proliferation or clinical outcome, which suggests that CGH does not necessarily give any additional information on the prognosis of the disease. MIB-1 index and TNM stage were associated with survival.

Adult↗
PubMed2004

A digital atlas of breast histopathology: an application of web based virtual microscopy.

AIMS: To develop an educationally useful atlas of breast histopathology, using advanced web based virtual microscopy technology. METHODS: By using a robotic microscope and software adopted and modified from the aerial and satellite imaging industry, a virtual microscopy system was developed that allows fully automated slide scanning and image distribution via the internet. More than 150 slides were scanned at high resolution with an oil immersion x 40 objective (numerical aperture, 1.3) and archived on an image server residing in a high speed university network. RESULTS: A publicly available website was constructed, http://www.webmicroscope.net/breastatlas, which features a comprehensive virtual slide atlas of breast histopathology according to the World Health Organisation 2003 classification. Users can view any part of an entire specimen at any magnification within a standard web browser. The virtual slides are supplemented with concise textual descriptions, but can also be viewed without diagnostic information for self assessment of histopathology skills. CONCLUSIONS: Using the technology described here, it is feasible to develop clinically and educationally useful virtual microscopy applications. Web based virtual microscopy will probably become widely used at all levels in pathology teaching.

Breast↗
PubMed2003

Membranous location of EGFR immunostaining is associated with good prognosis in renal cell carcinoma.

Epidermal growth factor receptor (EGFR) is a key factor in tumorigenesis. The association between EGFR expression and prognosis in renal cell carcinoma (RCC) is not clear. In our study of 134 RCCs, the cellular location of immunostaining was evaluated and patients with EGFR-positive tumours with prominent membranous staining had a good prognosis. Their overall survival was significantly longer (P=0.004) than that of patients with either EGFR-negative tumours or with mainly cytoplasmic staining. However, further studies on the different EGFR expression patterns in RCC are needed to clarify their role in the progression of the disease.

Adult↗
PubMed2003

Do temporal arteritis lesions contain bacterial DNA?

BACKGROUND: Temporal arteritis is a primary vascular inflammatory disease. The aetiology of temporal arteritis is unknown, but the influence of environmental factors such as infections has been suggested. MATERIALS AND METHODS: We used broad-range PCR, targeting conserved regions of the gene encoding for ribosomal RNA, to detect bacterial DNA in 27 temporal artery biopsies. Five uninvolved temporal arteries were also included. A lung sample of confirmed bacterial pneumonia served as a positive control. Inflammation was examined by histochemistry and light microscopy. RESULTS: The sensitivity of the broad-range PCR assay was 5.0 fg of DNA. Bacterial DNA sequences were neither detected in 27 temporal arteritis specimens nor in the normal temporal artery samples. However, bacterial DNA was successfully amplified from the lung sample of a subject with pneumonia. In addition, human DNA was amplified by primers for human beta-actin from all clinical specimens, suggesting lack of significant inhibitors of the molecular amplification reaction. Histochemistry showed signs of strong inflammation in the arteritis samples. CONCLUSIONS: The lack of detectable amounts of bacterial DNA suggests that viable bacteria do not have a role in chronic stages of temporal arteritis. However, these findings do not rule out the possibility of bacterial degradation products as stimulants of chronic inflammation, or of viable microbes as triggering factors of acute temporal arteritis.

Aged↗
PubMed2001

Cell cycle regulators (p21, p53, pRb) in oligodendrocytic tumors: a study by novel tumor microarray technique.

Using the novel tissue microarray technique, we studied immunohistochemical expression of cell cycle regulators p53, p21, pRb in 42 grade II oligodendrogliomas, 16 grade III anaplastic oligodendrogliomas, 10 primary and 4 recidive grade II oligoastrocytomas, 10 grade III oligoastrocytomas and 2 other grade II mixed gliomas. The p53 immunopositivity associated with malignant histology of the tumor (p = 0.01, Mann-Whitney test) and high pRb expression (p = 0.015). The p21 score associated strongly with histological grade (p < 0.001). The immunopositive tumors had a significantly higher rate of proliferation (p = 0.021). The p21 immunopositivity correlated positively with p53 immunopositivity: among the 33 p21 immunopositive tumors 30 (91%) were p53 immunopositive and only 3 were p53 immunonegative (p = 0.017). Patients with p21 immunonegative primary tumors had significantly better prognosis: among them 42 of the 46 (91%) survived, whereas only 18 of the 30 patients (60%) with p21 immunopositive primary tumors survived until the follow-up date (p = 0.0017). Statistical significance was reached in multivariate analysis as well (p = 0.01, exp(B) = 5.5). The pRb immunopositive tumors had higher proliferation rate than immunonegative tumors (p = 0.002). In multivariate variance analysis, comparing the effects of different regulatory proteins on cell proliferation, only the amount of pRb expression reached statistical significance (p = 0.004). In conclusion, the expression of p21 in oligodendrocytic tumors seems to be upregulated by p53 expression which rises with cell proliferation and malignancy as in attempt to halt cell cycle but seems to be overrun by other factors. The amount of p21 expression has independent prognostic significance and could be used in diagnosis to help the difficult evaluation of the malignancy potential of oligodendrogliomas and oligoastrocytomas.

Adolescent↗
PubMed2001

Mesangiocapillary glomerulonephritis caused by Puumala hantavirus infection.

Nephropathia epidemica induced by Puumala hantavirus typically causes acute reversible renal function impairment. A typical renal biopsy finding is acute tubulointerstitial nephritis with slight glomerular mesangial changes. We describe here 5 patients who developed the nephrotic syndrome during the convalescent phase of an otherwise typical acute febrile nephropathia epidemica. Renal biopsy of all patients disclosed type I mesangiocapillary glomerulonephritis (MCGN). A clinical remission of the nephrotic syndrome was observed in 4 patients during the follow-up period, and 1 entered into chronic renal failure. Three patients had microscopic hematuria and proteinuria and 2 elevated blood pressure at the latest assessment visit. No patient had clinical or laboratory findings compatible with chronic bacterial, parasitic or viral infections (hepatitis B or C), malignancies, or other disorders known to be associated with MCGN. In conclusion, Puumala hantavirus has to be added to the list of potential agents associated with type I MCGN. Further studies are necessary to establish the incidence of MCGN caused by various hantavirus infections.

Adult↗
PubMed2001

Predilection muscles and physical condition of raccoon dogs (Nyctereutes procyonoides) experimentally infected with Trichinella spiralis and Trichinella nativa.

The predilection muscles of Trichinella spiralis and T. nativa were studied in 2 experimental groups of 6 raccoon dogs (Nyctereutes procyonoides), the third group serving as a control for clinical signs. The infection dose for both parasites was 1 larva/g body weight. After 12 weeks, the animals were euthanized and 13 sampling sites were analysed by the digestion method. Larvae were found in all sampled skeleton muscles of the infected animals, but not in the specimens from the heart or intestinal musculature. Both parasite species reproduced equally well in the raccoon dog. The median density of infection in positive tissues was 353 larvae per gram (lpg) with T. spiralis and 343 lpg with T. nativa. All the infected animals had the highest larvae numbers in the carpal flexors (M. flexor carpi ulnaris). Also tongue and eye muscles had high infection levels. There were no significant differences in the predilection sites between these 2 parasite species. Trichinellosis increased the relative amount of fat, but not the body weight in the captive raccoon dogs. Thus, Trichinella as a muscle parasite might have catabolic effect on these animals.

Analysis of Variance↗
PubMed2000

Genetic aberrations in sporadic and neurofibromatosis 2 (NF2)-associated schwannomas studied by comparative genomic hybridization (CGH).

BACKGROUND: Schwannomas occur sporadically or in association with neurofibromatosis 2 (NF2), an autosomal dominant disorder, which predisposes to multiple schwannomas, meningiomas and spinal ependymomas, with bilateral vestibular schwannomas as the classic hallmark. As NF2 and sporadic schwannomas differ in some respect in their clinical and biological behavior we evaluated whether there are any differences in the distribution of genetic aberrations between NF2 and sporadic schwannomas. Our interest was also to verify whether secondary genetic alterations besides the loss of 22q could be detected in schwannomas. METHODS: We investigated DNA copy number changes in 25 schwannomas (12 NF2 and 13 sporadic schwannomas) using the comparative genomic hybridization (CGH) technique. Some chromosomal regions were further studied by LOH or FISH analysis. FINDINGS: CGH detected genomic abnormalities in 15 of 25 schwannomas (60%). The most common alteration was loss on 22q, found in 32% (8/25) of schwannomas. No consistent changes were detected in other chromosomal regions. The overall number of genetic aberrations was similar in NF2 and in sporadic schwannomas. INTERPRETATION: Our results support the present view that loss of chromosome 22q harboring the NF2 gene plays a universal role in the pathogenesis of schwannomas without consistent involvement of other chromosomal regions.

Adolescent↗