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Biomedical subjects

H Tuominen

Publications and source records attributed to H Tuominen.

At least 19 recordsLinked to original sources
PubMed2004

Hereditary dementia with intracerebral hemorrhages and cerebral amyloid angiopathy.

BACKGROUND: Deposition of the beta-amyloid peptide (Abeta) in neuritic plaques is a hallmark of Alzheimer disease (AD). Mutations in genes encoding amyloid precursor protein (APP) and presenilin 1 and 2 (PSEN1, PSEN2) are associated with increased accumulation of Abeta in neuritic plaques or in the walls of cerebral vessels. Intracerebral hemorrhage occasionally affects patients with AD. METHODS: A Finnish family with dementia in four generations and with frequent co-occurrence of dementia and intracerebral hemorrhage was identified. Clinical features of 14 family members with a cognitive decline were evaluated. All exons in genes encoding APP, PSEN1, PSEN2, cystatin C, transthyretin, gelsolin, and ITM2B were sequenced, and an association study of APP was conducted by identification of single-nucleotide polymorphisms. RESULTS: Neuropathologic examination revealed Alzheimer-type changes with Abeta in neuritic plaques and vessel walls, but the cognitive profile of the patients differed from that in AD, as the visuoconstructive functions and verbal fluency were well preserved even in the moderate stage of the disease. In addition to cognitive decline, five patients had had lobar intracerebral hemorrhages and one was diagnosed with hemosiderin deposits in MRI, suggesting previous cerebral microbleeds. No causative mutations were identified in candidate genes associated with amyloid diseases, but linkage to APP region could not be entirely excluded. CONCLUSIONS: The family presents an autosomal dominant form of beta-amyloidogenic disease that resembles the Italian, Flemish, and Iowa types of AD. No amyloidogenic mutations were identified, but the role of the APP region could not be entirely excluded.

Adult↗
PubMed2001

Expression and glycosylation studies of human FGF receptor 4.

Fibroblast growth factor receptor subtype 4 (FGFR4) has been shown to have special activation properties and just one splicing form, unlike the other FGFRs. FGFR4 overexpression is correlated with breast cancer and therefore FGFR4 is a target for drug design. Our aim is to overexpress high amounts of homogeneous FGFR4 extracellular domain (FGFR4(ed)) for structural studies. We show that baculovirus-insect cell-expressed FGFR4(ed) is glycosylated on three (N88, N234, and N266) of the six possible N-glycosylation sites but is not O-glycosylated. The deglycosylated triple mutant was expressed and had binding properties similar to those of glycosylated FGFR4(ed), but was still heterogeneous. Large amounts of FGFR4(ed) have been produced into inclusion bodies in Escherichia coli and refolded at least partly correctly but the refolded E. coli-produced FGFR4(ed) still aggregates.

Amino Acid Sequence↗
PubMed2001

Isolated neurosarcoidosis - MR findings and pathologic correlation.

Neurosarcoidosis is a diagnostic challenge, especially if systemic symptoms are absent. We present a 49-year-old woman with isolated neurosarcoidosis. The main symptom was loss of vision in the left eye. Brain MR imaging showed 6 high-signal white matter lesions frontotemporally on proton density and T2-weighted turbo spin-echo images. Coronal fat-saturated turbo FLAIR images of the orbits showed a swollen left optic nerve with increased signal intensity, which finding has not been previously published in sarcoid optic neuropathy. A control MR examination showed meningeal enhancement of the left optic nerve and leptomeningeal enhancing lesions around the brain stem. Spinal MR revealed leptomeningeal enhancement throughout the spinal cord and asymptomatic enhancing cauda equina lesions, mimicking subarachnoid tumour seeding, and an enhancing nerve root mass at Th12/L1. Biopsy of the latter lesion revealed non-caseating granulomas consistent with sarcoidosis.

Brain↗
PubMed2000

Cambial-region-specific expression of the Agrobacterium iaa genes in transgenic aspen visualized by a linked uidA reporter gene.

The level of indole-3-acetic acid (IAA) was locally modified in cambial tissues of transgenic aspen (Populus tremula L. x Populus tremuloides Michx.). We also demonstrate the use of a linked reporter gene to visualize the expression of the iaa genes. The rate-limiting bacterial IAA-biosynthetic gene iaaM and the reporter gene for beta-glucuronidase (GUS), uidA, were each fused to the cambial-region-specific Agrobacterium rhizogenes rolC promoter and linked on the same T-DNA. In situ hybridization of the iaaM gene confirmed that histochemical analysis of GUS activity could be used to predict iaaM gene expression. Moreover, quantitative fluorometric analysis of GUS activity allowed estimation of the level of de novo production of IAA in transgenic lines carrying a single-copy insert of the iaaM, uidA T-DNA. Microscale analysis of the IAA concentration across the cambial region tissues showed an increase in IAA concentration of about 35% to 40% in the two transgenic lines, but no changes in the radial distribution pattern of IAA compared with wild-type plants. This increase did not result in any changes in the developmental pattern of cambial derivatives or the cambial growth rate, which emphasizes the importance of the radial distribution pattern of IAA in controlling the development of secondary xylem, and suggests that a moderate increase in IAA concentration does not necessarily stimulate growth.

Blotting, Northern↗
PubMed2000

Ozone-sensitive arabidopsis rcd1 mutant reveals opposite roles for ethylene and jasmonate signaling pathways in regulating superoxide-dependent cell death.

We have isolated a codominant Arabidopsis mutant, radical-induced cell death1 (rcd1), in which ozone (O(3)) and extracellular superoxide (O(2)(*)-), but not hydrogen peroxide, induce cellular O(2)(*)- accumulation and transient spreading lesions. The cellular O(2)(*)- accumulation is ethylene dependent, occurs ahead of the expanding lesions before visible symptoms appear, and is required for lesion propagation. Exogenous ethylene increased O(2)(*)--dependent cell death, whereas impairment of ethylene perception by norbornadiene in rcd1 or ethylene insensitivity in the ethylene-insensitive mutant ein2 and in the rcd1 ein2 double mutant blocked O(2)(*)- accumulation and lesion propagation. Exogenous methyl jasmonate inhibited propagation of cell death in rcd1. Accordingly, the O(3)-exposed jasmonate-insensitive mutant jar1 displayed spreading cell death and a prolonged O(2)(*)- accumulation pattern. These results suggest that ethylene acts as a promoting factor during the propagation phase of developing oxyradical-dependent lesions, whereas jasmonates have a role in lesion containment. Interaction and balance between these pathways may serve to fine-tune propagation and containment processes, resulting in alternate lesion size and formation kinetics.

Arabidopsis↗
PubMed1999

Accurate and high resolution in situ hybridization analysis of gene expression in secondary stem tissues.

Accurate in situ hybridization analysis in secondary stem tissues of plants has been hindered by specific characteristics of these tissues. First, secondary cell walls non-specifically bind probes used for in situ hybridization thus preventing gene expression analysis in the lignified regions of the stem, such as the xylem. Second, the mRNA in the cambial meristem and its recent derivatives are prone to inadequate fixation when conventional techniques are used. Here we describe an in situ hybridization technique which uses fast freezing and freeze substitution to cryoimmobilize the mRNA followed by embedding in a methacrylate resin for high-resolution analysis of gene expression. By using a transgenic poplar line harbouring rolC:uidA, rolC:iaaM, the gene expression pattern could be compared with histochemical GUS staining. This in situ hybridization technique results in superior preservation of cellular contents, retention of mRNA in all cell types in the poplar stem, a significant reduction of non-specific binding to secondary cell walls and a resolution not previously possible in secondary tissues. This technique will be particularly valuable for the expression analysis of genes involved in xylogenesis and wood formation.

Gene Expression↗
PubMed1997

Multicellular origin of tenascin in skin tumors--an in situ hybridization study.

Tenascin mRNA expression was studied by an in situ hybridization method in 27 skin tumors. Tenascin synthesis was increased in all skin tumors when compared to uninvolved skin but there was variation in the site of cellular synthesis between different types of tumors. In melanocytic nevi and precancerous keratinocyte lesions, tenascin seemed to be of epidermal or stromal origin. In basal cell carcinoma, squamous cell carcinoma and malignant melanoma, there was tenascin synthesis also in tumor cells. These findings are in concordance with earlier studies which suggest a role of tenascin as an anti-adhesive and motility-promoting factor in malignant skin tumors.

Basal Cell Carcinoma↗
PubMed1996

Matrix metalloproteinase-2 (72 kD type IV collagenase) expression occurs in the early stage of human melanocytic tumour progression and may have prognostic value.

Matrix metalloproteinase-2 (MMP-2), a member of the matrix metalloproteinase family, participates in degradation of the pericellular and extracellular matrix during neoplastic growth and metastasis. Experimental data have substantiated its role in melanoma invasion, but there is no information at present concerning its expression in histological specimens from human melanocytic tumors. This study describes the occurrence and immunolocalization of MMP-2 in human melanocytic lesions, defining distinct steps in melanoma progression. Paraffin-embedded sections from 118 melanocytic lesions were immunostained using a specific antibody to 72 kD type IV collagenase. The material included 34 common naevocellular naevi, 14 dysplastic naevi, 21 in situ melanomas, 20 primary malignant melanomas, and 29 melanoma metastases. Intracytoplasmic MMP-2 immunoreactive protein was found in the 'naevocytic nests' of common naevi, in junctional naevus cells, and in melanoma cells. The surrounding normal skin stained negatively, except for occasional macrophages, sweat glands, and hair follicles. The number of MMP-2-positive cells increased with decreasing architectural organization and increasing atypia in the melanocytic lesions. The MMP-2 positivity in the primary and subcutaneous melanoma lesions correlated with later haematogenous metastasis. The data suggest that MMP-2 expression is an early event in melanocytic tumour progression, but is nevertheless prognostic for haematogenous metastasis in melanoma.

Adult↗
PubMed1996

Non-erythroid spectrin (fodrin) in cutaneous tumours: diminished in cell membranes, increased in the cytoplasm.

The expression and distribution of non-erythroid spectrin (alpha-fodrin), a basic protein of the cell membrane skeleton, was investigated by immunohistochemical methods in 42 cutaneous tumours. The suprabasal keratinocytes of the normal epidermis showed plasma membrane-associated spectrin. The basal cells of the normal epidermis, seborrhoeic keratosis, and basal cell carcinoma, revealed both intracytoplasmic and membrane-bound spectrin. In squamous cell carcinoma, the expression of spectrin was heterogeneous and mostly intracytoplasmic. The dysplastic cells of solar keratosis expressed no spectrin at all. In various types of melanocytic naevi, intracytoplasmic and discontinuous membrane-bound spectrin was found in most tumour cells. Malignant melanomas showed a heterogeneous intracytoplasmic staining for spectrin, or were negative. The results indicate a diminished amount, or a total lack, of membrane-bound spectrin with increasing depolarization and proliferation of cells in solar keratosis and pigment cell tumours, but a partial preservation in polarized cells of basal cell carcinoma. The increase and heterogeneity, in cytoplasmic spectrin, of squamous cell carcinoma and malignant melanoma seemed to be associated with the less differentiated, invasive cells of these malignant tumours.

Basal Cell Carcinoma↗
PubMed1996

Gastric cancer: surgical management and prognosis.

The experience of the Department of Surgery of Oulu University Hospital, Finland, in the treatment of 203 consecutive patients (129 men and 74 women, mean age 64.9 years) with primary gastric cancer during the five-year period from 1983 to 1987 is reviewed. 196 (96.6%) patients underwent surgery; radical gastrectomy with limited lymphadenectomy in 88 (43.3%) cases, palliative gastric resections in 47 (23.3%) cases and symptomatic bypass procedures in 27 (13.3%) cases. Postoperative complications occurred more frequently after total than after subtotal gastrectomy. Overall postoperative mortality was 9.2%. The five-year survival was 21.1% for all patients and 45.5% for curatively operated patients. Univariate analysis indicated that tumour size, location, gross appearance, degree of gastric wall invasion, presence of lymph node and/or distant metastases, and operative procedures were the significant prognostic factors of survival. In a Cox multivariate analysis on the T stage and presence of distal metastases independently affected survival. Our results show that besides early detection, the standardisation of surgical procedures (extent of gastrectomy and lymphadenectomy) as well as substantial decrease in postoperative complications and mortality rates are of importance in the improvement of the outcome of surgery for gastric cancer.

Adult↗
PubMed1995

Biphasic formation of inositol phosphates in opsonized zymosan-stimulated human neutrophils.

Stimulation by serum-opsonized zymosan (SOZ) typically causes a biphasic rise in the cytosolic free Ca2+ concentration ([Ca2+]i) of human neutrophils. It consists of an initial slow Ca2+ release from internal pools lasting for 60 s, followed by a rapid but sustained influx of Ca2+. It was the aim of this study to elucidate the underlying mechanism of this atypical Ca2+ response. For this reason we analysed the production of inositol phosphates (InsPs) in myo-[3H]inositol labelled cells. Stimulation by SOZ within 10 s transiently elevated inositol trisphosphate (InsP3) by 1.50-fold. This response was followed by a second, more sustained 1.55-fold rise in InsP3 by 90 s. A similar, biphasic pattern of inositol tetrakisphosphate (InsP4) formation with 1.15- and 1.35-fold increases, respectively, was observed. The SOZ-induced formation of InsP3 was unaffected by the removal of extracellular Ca2+ by 1.4 mM EGTA. In contrast, the early accumulation of InsP4 was stronger and more prolonged and no second rise over the baseline level was seen in the absence of extracellular Ca2+. Under these conditions, the sudden exposure of Fura-2 AM loaded, SOZ-stimulated neutrophils to extracellular Ca2+ at a time point where InsP4 was the predominant InsP resulted in a marked increase in [Ca2+]i. Recalcification at a time point when InsP3 was the major InsP had no effect on [Ca2+]i. These findings suggest that in SOZ-stimulated neutrophils (1) the transient, first accumulation of InsP3 mediates the slow Ca2+ release from internal pools, and (2) the second, more pronounced formation of InsP4 triggers the Ca2+ influx.(ABSTRACT TRUNCATED AT 400 WORDS)

Blood↗
PubMed1994

Does protein kinase C regulate receptor agonists-mediated elevation in the cytosolic Ca2+ in human neutrophils?

The feedback regulation of elevated cytosolic free Ca2+ concentrations ([Ca2+]i) by protein kinase C (PKC) in neutrophils was studied by two approaches. First, the PKC-activity was induced by phorbol 12-myristate 13-acetate (PMA) before the stimulation of Ca2+-signal with N-formyl-methionyl-leucyl-phenylalanine and serum-opsonized zymosan particles. Pretreatment of cells with PMA inhibited agonists-dependent Ca(2+)-transients. This inhibition was reversed by staurosporine. Second, the PKC-activity was induced simultaneously with the Ca(2+)-signal by the receptor agonists. In these conditions staurosporine had no effect on the Ca(2+)-response. In addition, the enhancement of PKC-activity, obtained by accumulating the endogenous PKC-activator diacylglycerol (DAG) with a DAG-kinase inhibitor, failed to change the agonists-stimulated elevations of [Ca2+]i. It is concluded that activation of PKC by PMA inhibits neutrophil Ca(2+)-responses, whereas receptor-mediated activation of PKC does not yield a negative feedback in elevated [Ca2+]i.

Alkaloids↗
PubMed1994

Seasonal changes in bud dormancy in relation to bud morphology, water and starch content, and abscisic acid concentration in adult trees of Betula pubescens.

Annual cycles of change in bud morphology, bud burst ability, abscisic acid (ABA) concentration, and starch and water content were studied in mid-crown terminal buds of short shoots and underground basal buds of Betula pubescens Ehrh. In particular, we investigated the roles of ABA and bud water content in the regulation of bud growth. Basal buds differed morphologically from terminal buds of short shoots in that their leaf initials did not develop into embryonic foliage leaves and their total size did not increase significantly during summer. Bud burst ability, measured by forcing detached short shoots and stumps under controlled conditions, was maintained in the basal buds throughout the year, whereas the terminal buds of short shoots remained dormant until October, thereafter their bud burst ability increased gradually and reached a maximum in March-April. The ABA concentration of the basal buds was relatively constant throughout the sampling period (1-3 micro g g(DW) (-1)), whereas that of the terminal buds of short shoots, which was much higher (5-10 micro g g(DW) (-1)), showed a distinct seasonal cycle with a maximum from August to November. Bud ABA concentration decreased during the first 10 days of forcing, especially in basal buds. In both bud types, the amount of starch increased toward the autumn, declined in November, and was negligible in the terminal buds of short shoots between January and March, but in April, the amount was high again in both bud types. Water content varied characteristically in both bud types, although more distinctly in the terminal buds of short shoots, with an increase in spring before bud burst and a decrease during the summer until September. The significant morphological and physiological differences between the mid-crown terminal buds of short shoots and the underground basal buds may partly explain the characteristic growth habit of the basal buds and their development into coppice shoots after cutting the tree. The results also indicate a role for ABA in maintaining dormancy of the terminal buds of short shoots and emphasize the relationship between tissue water status and ABA concentration.

Journal Article↗
PubMed1994

Increased tenascin expression in melanocytic tumors.

Tenascin is a large extracellular matrix glycoprotein which is widely distributed in normal, hyperplastic and neoplastic tissues. Its function is unknown but it has been associated with the epithelial-stromal interactions, such as cell adhesion and movement which take place, e.g. in morphogenesis, cellular proliferation and neoplasia. In this study, we investigated tenascin expression in 70 benign, dysplastic and malignant melanocytic tumors by using immunohistochemistry and monoclonal anti-tenascin 143DB7C8 antibody on paraffin sections. In all types of benign nevi, both intradermal, compound and junctional, there was a moderate expression of tenascin at the dermoepidermal junction and in the papillary dermis. In dysplastic nevi, the fibrotic areas in the papillary dermis also showed a moderate staining for tenascin. Invasive malignant melanomas showed the strongest expression of tenascin. In addition to the staining at the dermo-epidermal junction and in the papillary dermis, there was a variable expression of tenascin in the reticular dermis. Intracytoplasmic tenascin was detected both in primary melanomas and melanoma metastases. In conclusion, we have shown that tenascin expression is moderately increased in benign and dysplastic melanocytic tumors and greatly increased in malignant melanomas and melanoma metastases. The function of tenascin may be related to the cellular-stromal interactions and it is possibly associated with the proliferation and spread of the melanocytic tumors.

Biopsy↗
PubMed1994

Cell-type related and spatial variation in the expression of integrins in cutaneous tumors.

Integrins constitute a group of transmembrane proteins which mediate cell-cell and cell-matrix interactions. Previous studies have shown both increased and decreased expression of integrins in relation to malignancy and invasion. In the present study, we investigated integrin distribution in cutaneous tumors by using monoclonal antibodies on frozen tissue sections. Antibodies to integrin subunits alpha v, alpha 3, alpha 4, alpha 5, alpha 6, beta 1 and beta 3 were used. The study was designed to explore (i) the association between integrin expression and the tumor type, and (ii) the effect on the integrin expression of the location of the tumor, i.e. whether it grows intraepidermally or within various compartments of the dermis (papillary or reticular). Beta 1, beta 3 and alpha 3 were strongly or moderately expressed in the epithelial and stromal cells of basal cell carcinomas (BCC), seborrheic keratoses, solar keratoses, dermatofibromas (DF), and showed a variable expression in the nevic cells of benign and dysplastic nevocellular nevi. alpha v and in alpha 5 appeared strongly expressed in the stromal cells of BCC and DF, while only a focal, often weak staining was seen in nevic cells and in the epithelial cells of BCCs. In some nevocellular nevi, they were only expressed, together with alpha 4, in the deep-seated nevic cells in the reticular dermis. alpha 6 was expressed by tumor cells of BCCs and nevocellular nevi only within the dermo-epidermal junction. In seborrheic keratosis and solar keratosis a basement membrane-associated staining pattern for alpha 6 was seen in the basal cell layer, with focal discontinuities in solar keratosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1994

Generation of cartilage from auricular and rib free perichondrial grafts around a self-reinforced polyglycolic acid mould in rabbits.

The generative potential of free perichondrial grafts from rabbit auricular and rib cartilage around a self-reinforced polyglycolic acid (SR-PGA) rod was examined in eight growing rabbits. A 15 x 15 mm perichondrial graft was dissected away from the posterior side of each auricular cartilage. One graft was wrapped around a 1.1 x 10 mm SR-PGA rod and the other served as a control and was shaped into a tube without an implant. Fifth rib cartilages were then resected subperichondrially on both sides. The remaining perichondrium on the other side was wrapped around a 1.1 x 10 mm SR-PGA rod, while the other served as a control and was shaped into a tube without an implant. All the grafts were placed inside pectoralis major muscles. Grafts were biopsied six weeks postoperatively. Neocartilage formation was seen in all grafts with one exception on both the implant and control sides. It formed a tube-like structure around the implant in four cases after grafting of auricular perichondrium and in three cases after grafting of rib perichondrium. New bone formation was also observed. SR-PGA implants did not seem to disturb the generative potential of perichondrium.

Animals↗