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J Peltonen

Publications and source records attributed to J Peltonen.

At least 73 records · Page 4Linked to original sources
PubMed1995

A fibroblast cell line cultured from a hypertrophic scar displays selective downregulation of collagen gene expression: barely detectable messenger RNA levels of the pro alpha 1(III) chain of type III collagen.

The present study was designed to investigate the expression of type I, III and VI collagens by a fibroblast cell line initiated from a hypertrophic scar. The same tissue has previously been demonstrated to display markedly elevated expression of type I and III collagen mRNAs in vivo. Unexpectedly, slot-blot and Northern hybridizations revealed a barely detectable steady-state level of pro alpha 1(III) collagen chain mRNA in cultured hypertrophic scar fibroblasts. The levels of pro alpha 1(I) and alpha 2(VI) collagen chain mRNAs were essentially the same in fibroblasts cultured from hypertrophic scar and in fibroblasts cultured from normal skin. However, Northern blot analyses indicated that the ratio of 5.8 kb to 4.8 kb species of pro alpha 1(I) collagen mRNA was slightly reduced in fibroblasts originating from the hypertrophic scar compared to that in normal fibroblasts. When normal fibroblasts were incubated in conditioned medium from hypertrophic scar cultures, the expression of pro alpha 1(III) collagen chain mRNA decreased to a markedly lower level. Our studies suggest that collagen synthesis by fibroblasts in hypertrophic scars is stimulated by humoral factors which are active only in vivo. Furthermore, the results suggest that fibroblasts cultured from hypertrophic scar display a selective downregulation of different collagen genes and that this downregulation is exerted through an autocrine mechanism.

Adult↗
PubMed1995

An experimental model for non-union in rats.

Few studies of the biological changes which occur in impaired fracture repair and non-union have been carried out, and creating an appropriate model for advanced biochemical studies of non-union has proved to be a demanding task. This paper presents a standardized experimental model for producing non-union in rat femurs, for use in biochemical studies of non-union. A mid-diaphyseal fracture with a rotationally unstable fixation was performed in rats with a mean weight of over 330 g and mean age of over 10 weeks. Radiologically and histologically (Alcian blue and Safranin O stainings) the signs of undisturbed fracture healing were observed until 3 weeks after the fracture. Thereafter there was evidence that chondrocytic activity ceased, with no signs of formation of calcifying bridging callus. From the seventh week onwards, all elements necessary for a calcifying callus were lost; and the histological picture tended to be of scar tissue bond between the fracture ends.

Animals↗
PubMed1995

Lesional psoriatic epidermis displays reduced neurofibromin immunoreactivity.

Neurofibromin enhances the inactivation of protooncogene p21ras and has been suggested to function as a regulator of cell growth and differentiation. In normal skin, neurofibromin is particularly abundant in the basal keratinocytes of epidermis. The present study utilized antibodies raised against two synthetic peptides corresponding to different regions of neurofibromin. One of the antibodies recognized all forms of neurofibromin and the other was specific for type II neurofibromin. The following specimens were analyzed for neurofibromin immunoreactivity: 1) skin of apparently healthy volunteers, 2) active lesions of 15 psoriatic patients, 3) apparently healthy skin of the same patients at the time of the active phase of the disease, and 4) the previously lesional areas after anti-psoriatic treatment of the same patients. The presence of neurofibromin mRNA in normal epidermis and in keratinocytes cultured from normal skin was demonstrated by reverse transcriptase-polymerase chain reaction or by Northern hybridization. In marked contrast to normal epidermis, active psoriatic lesions were characterized by a weak immunosignal for types I and II neurofibromin in the basal cell layer of the epidermis. Previously lesional, clinically healed areas displayed variable, yet clearly detectable, expression of neurofibromin. Our results demonstrate that the epidermis of psoriatic lesions displays reduced immunostaining for type I and II neurofibromins compared to normal epidermis, and that neurofibromin immunoreactivity is partially restored concomitant with clinical healing of the lesions. The question whether the changes in neurofibromin expression in psoriasis are causal or consequential with respect to the pathogenesis of psoriasis remains to be elucidated.

Adolescent↗
PubMed1995

Effects of metformin treatment on glucose transporter proteins in subcellular fractions of skeletal muscle in (fa/fa) Zucker rats.

1. The present study was designed to clarify the cellular mechanism through which the antihyperglycaemic drug, metformin, exerts its effects. For this purpose the contents of glucose transporter protein isoforms GLUT1 and GLUT4 were measured in plasma membrane and intracellular membrane fractions of skeletal muscle obtained from genetically obese, insulin-resistant Zucker rats. 2. Hindlimb muscles were dissected from metformin-treated (300 mg kg-1 day-1, p.o., for 12 days) and control rats in basal treatment state, and after acute stimulation with insulin (22 u kg-1, i.p.). Since metformin treatment reduces food intake, we also used a pair-fed control group to investigate the effects of altered insulinaemia per se. Glucose transporter levels were analysed by Western blot and slot blot-techniques. In addition, 2-deoxy-[14C]-glucose uptake in isolated muscle strips was evaluated. 3. No changes were noted in the contents of GLUT1 proteins in any of the subcellular fractions after metformin treatment. The contents of GLUT4 in subcellular fractions were not altered in the basal treatment state. After acute insulin exposure the content of GLUT4 in the intracellular membrane fraction declined significantly in the metformin-treated group, while no significant effect was seen in the plasma membrane fraction. In agreement with these results, metformin treatment did not alter 2-deoxyglucose uptake into isolated muscle strips. 4. In conclusion, the present study does not support the concept that metformin would enhance translocation of glucose transporter proteins from the intracellular compartment to the plasma membrane in skeletal muscle in vivo.

Animals↗
PubMed1995

Neurofibromin: expression by normal human keratinocytes in vivo and in vitro and in epidermal malignancies.

BACKGROUND: Neurofibromin is the product of the NF1 gene, the mutations of which have been linked with type 1 neurofibromatosis. The expression of neurofibromin in human skin has not been analyzed in detail. EXPERIMENTAL DESIGN: Polyclonal Ab were raised against synthetic peptides corresponding to three different sites of neurofibromin. One of the Ab selectively recognized type II neurofibromin. The localization of neurofibromin was first studied in normal human skin. Further studies concentrated on neurofibromin expression in basal cell and squamous cell carcinomas. Reverse transcription-PCR (RT-PCR) and molecular hybridizations and immunocytochemistry were used to characterize the expression of neurofibromin in cultured keratinocytes. RESULTS: All neurofibromin-specific Ab immunolabeled the epidermis. The basal keratinocytes displayed the most prominent immunosignal for type II neurofibromin. RT-PCR demonstrated the presence of both type I and II neurofibromin mRNA transcripts in cultured keratinocytes. Keratinocytes induced to differentiate and to arrest division by a high (1.4 mM) Ca2+ concentration of the culture medium displayed a down-regulation of neurofibromin expression at the mRNA and protein levels. This was most strikingly demonstrated by a reduction of immunoreactivity for type II neurofibromin. Basal cell carcinomas displayed a weak immunosignal for type II neurofibromin. In contrast, particularly the central areas of squamous cell carcinoma, islands were intensely immunolabeled. CONCLUSIONS: The results suggest that neurofibromin acts as a regulator of the basal keratinocytes in normal skin and that cultured keratinocytes offer a human model for studies aimed to elucidate the regulation of neurofibromin gene expression. Furthermore, aberrations in neurofibromin expression may play a role in the pathogenesis of epidermal cancers.

Amino Acid Sequence↗
PubMed1994

Normal and hypertrophic scars: quantification and localization of messenger RNAs for type I, III and VI collagens.

The expression of type I, III and VI collagens was studied in nine normal and two hypertrophic scars using slot-blot and in situ hybridization techniques. Slot-blot hybridization indicated that the steady-state levels of pro alpha 1(I) and pro alpha 1(III) collagen chain mRNAs were moderately elevated in two of the nine normal scars, whereas the two hypertrophic scars analysed displayed markedly elevated mRNA levels when compared with normal skin. The mRNA levels of alpha 2(VI) collagen chain were only slightly elevated in both types of scars studied. In situ hybridization was most informative when applied to hypertrophic scars. These lesions were characterized by the presence of intense hybridization signals for type I and III collagen mRNAs, and a moderate signal for type VI collagen mRNA, in nodules which were located in the upper dermis on each side of the original wound. This may explain, in part, why hypertrophic scars rise above the level of the surrounding skin. The results of the present study are in marked contrast to our previous findings on collagen gene expression in keloids and neurofibromas, in which the steady-state levels of type VI and I collagen mRNAs in particular were shown to be elevated. Thus, our results emphasize that distinct molecular mechanisms are operative in the development of clinically different dermal fibrotic conditions, such as normal and hypertrophic scars, keloids and neurofibromas.

Adolescent↗
PubMed1994

Expression of type I, III, and VI collagen mRNAs in experimentally injured porcine intervertebral disc.

Young domestic pigs were incised with a scalpel blade into the anterior part of annulus fibrosus of lumbar discs in order to study the reparative processes in the annulus fibrosus and the secondary reactions in the nucleus pulposus. Northern and slot-blot hybridizations were used to investigate type I, III, and VI collagen gene expression in the disc tissue. For this purpose a method for RNA isolation was modified so as to be applicable to the intervertebral disc, which has a low cell density and a high proteoglycan content in its extracellular matrix. The amount of total RNA was found to be very low, particularly in the nucleus pulposus. Intact RNA could be isolated from most parts of the injured discs, but only from the outer annulus of the control discs. Hybridizations showed that healing of the wound in the annulus fibrosus involves an increase in the synthesis of particularly type I and type III collagens. However, no changes in the collagen gene expression were detectable in the nucleus pulposus two weeks after the injury.

Animals↗
PubMed1994

Connective tissue metabolism in diabetic peripheral nerves.

Diabetes mellitus is associated with multiple connective tissue changes, such as generalized thickening of basement membranes. These alterations are suspected of contributing to the development of diabetic long-term complications encountered in many organs, including kidney, eye and peripheral nerves. The latter tissue, however, has gained relatively little attention with respect to connective tissue changes associated with diabetes. The morphological alterations of connective tissue in the diabetic peripheral nerve include thickening of basement membranes, increased diameter of endoneurial collagen fibrils, and accumulation of microfibrillar material. Recent studies have further elucidated the changes in the extracellular matrix of diabetic nerves and the molecular mechanisms underlying these alterations. For instance, elevated glucose concentrations modulate the expression of several proteins of the extracellular matrix in cultured nerve-derived connective tissue cells. In this article, we review the recent progress in the field of connective tissue alterations in diabetes and particularly in the diabetic peripheral nerve.

Connective Tissue↗
PubMed1993

Expression of glucose transporter 1 in adult and developing human peripheral nerve.

Northern hybridization of total RNA isolated from adult human sciatic nerve demonstrated a readily detectable hybridization signal for glucose transporter 1 (GLUT 1) mRNA. Western blot analysis demonstrated that GLUT 1 proteins extracted from adult human and from mature rat sciatic nerves had different electrophoretical mobilities. The migration positions of human and rat GLUT 1 proteins corresponded to 60-70 kDa and 55-60 kDa, respectively, as estimated by markers with known molecular masses. Indirect immunofluorescence staining localized GLUT 1 to the perineurium in the adult human sciatic nerve. Only a few endoneurial capillaries of human adult nerve stained positively for GLUT 1, which was in contrast to rat peripheral nerve where most endoneurial capillaries were positive for GLUT 1. In developing human nerves, the staining pattern for GLUT 1 was markedly different from that of the adult nerves: at 14 weeks, the perineurial cells were entirely negative for GLUT 1. Between 22 and 26 weeks of gestation, the staining reaction for GLUT 1 in the perineurium became markedly more prominent, and by 35 weeks the intense perineurial staining resembled that observed in the adult human nerves. In contrast to adult nerves, both endo- and epineurial blood vessels stained intensely for GLUT 1 in the fetal samples. Thus, the immunoreactivity for GLUT 1 in the perineurium seems to increase concomitant with the maturation of barrier properties of perineurium, whereas the transient expression of GLUT 1 in the vasculature of developing nerve may have a specific role in the proliferating endothelial cells.

Adolescent↗
PubMed1993

Basement membranes during development of human nerve: Schwann cells and perineurial cells display marked changes in their expression profiles for laminin subunits and beta 1 and beta 4 integrins.

The formation of the connective tissue compartments of human sciatic and tibial nerves was studied with special reference to the maturation of the basement membranes during foetal development (11-35 weeks of gestation). All Schwann cells were surrounded by continuous basement membranes as early as at week 11, while the perineurial cells became covered by basement membranes gradually between weeks 17 and 35, as estimated by electron microscopy. The first laminin subunits detectable within the nerve were the B1, B2 and M chains. These laminin subunits were present in Schwann cell basement membrane zone at week 11, and in the perineurium at week 17 and later. Laminin A and S chains were first detected at 26 weeks in the perineurium, and at a later stage (35 weeks) on Schwann cells. In mature nerves, all these five laminin chains could be demonstrated in both Schwann cell and perineurial cell basement membrane zones, although A, S and B2 chains predominated in the perineurium, and M, B1 and B2 were the predominant chains in Schwann cell basement membranes. Beta 1 and beta 4 integrins were expressed by all Schwann cells in samples from the youngest foetuses (11-17 weeks). At 22-35 weeks, however, only a subpopulation of Schwann cells stained positively for beta 1 and beta 4 integrins. Perineurial cells expressed beta 1 integrins at all ages studied. Staining for beta 4 integrin in perineurium became detectable and intensified concomitant with the formation of structural basement membranes. The results demonstrate that Schwann cells and perineurial cells change their laminin and integrin expression profiles during the maturation of peripheral nerve.

Antigens↗
PubMed1993

Interrelations between power, force production and energy metabolism in maximal leg work using a modified rowing ergometer.

The dependence of power on aerobic and anaerobic energy metabolism and on force production was studied in maximal leg exercise. National and international level male rowers (n = 9) performed four modified (legs-only) rowing ergometer exercises: a progressive test, 2-min (T2), 12-min (T12) and 6-min (T6) all-out tests. In T2, significant correlations were observed between power in T2 (PT2) and oxygen debt (r = 0.83, P < 0.05) and between PT2 and average force production (Fav) during the last 30 s (r = 0.85, P < 0.05). These parameters explained 93% of the variation in PT2. The highest correlations between power in T6 (PT6) and physiological parameters were as follows: maximal oxygen uptake (VO2 max: r = 0.87, P < 0.01), blood bicarbonate concentration before the test ([HCO3-before]: r = 0.85, P < 0.05) and blood lactate concentration on anaerobic threshold (BLaAnT: r = -0.82, P < 0.05). Together, these parameters explained 92% of the variation in PT6. In T12, the total power (PT12) correlated with power of anaerobic threshold (PAnT: r = 0.95, P < 0.001) and with the highest VO2 value in this test (VO2 peak: r = 0.92, P < 0.001). These two parameters explained 96% of the variation in PT12. The decrease of at least one of the force parameters during each test was taken as a sign of fatigue. The decline in force was compensated for by an increase in stroke rate at the end of T6 and T12 (P < 0.01, P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Effects of distraction and compression on proliferation of growth plate chondrocytes. A study in rabbits.

An external fixation device was applied across the distal femoral physis in 30 rabbits, and distraction or compression was performed for 3-21 days; either no operation or a sham-operation was performed on the contralateral side. Proliferating cells were labeled with 5-bromo-2'-deoxyuridine, a thymidine analogue, and subsequently localized in decalcified histologic sections using a specific monoclonal antibody. The height of the proliferative and hypertrophic zones was increased after distraction; additionally, fracture-separation through the hypertrophic zone or at the junction of the physis and metaphysis was seen in 13 of the 15 specimens. Labeled cells were encountered only in the proliferative zone in all specimens except after early distraction, where labeled chondrocytes were seen close to the separation gap in the hypertrophic zone, too. Distraction had no effect on the number of labeled cells. A reduction in the height of the proliferative and hypertrophic zones occurred after compression, and the number of proliferating chondrocytes decreased.

Animals↗
PubMed1993

Expression of laminin isoforms by peripheral nerve-derived connective tissue cells in culture. Comparison with epitope distribution in normal human nerve and neural tumors in vivo.

BACKGROUND: Laminins are a family of multifunctional glycoproteins that play a role in various aspects of cell biology. Three different isoforms of laminin have been described, and each comprises a molecule consisting of three subunit polypeptides, the A, B1, B2, M or S chain. EXPERIMENTAL DESIGN: The expression pattern of laminin isoforms was studied by indirect immunofluorescence staining of human peripheral nerve in situ or cell cultures derived from such nerve by using monoclonal antibodies recognizing the subunit epitopes. RESULTS: Selective expression of the subunit polypeptides of laminin isoforms in endoneurium and perineurium was demonstrated. Specifically, an intense immunoreaction for A, B2 and S chain epitopes could be detected in perineurium, whereas endoneurium revealed the presence of B1, B2, M and S chains. Examination of the laminin isoform expression in perineurial cells, Schwann cells, and fibroblasts in cultures derived from normal human nerve indicated, however, that these cells under in vitro conditions were capable of expressing all five laminin chains. Cutaneous neurofibromas, tumors characterized by the presence of mixed cell populations consisting of Schwann cells, perineurial cells, and fibroblasts, demonstrated the expression of B1, B2 and M chain epitopes, whereas only a weak immunostaining could be detected with antibodies recognizing the A and S chains. Similar observations were made on schwannomas, a Schwann cell tumor. CONCLUSIONS: Collectively, the observations of this study attest to the plasticity of neural-derived connective tissue cells with respect to laminin isoform expression. Such plasticity may relate to the cell-cell and cell-matrix interactions during development of peripheral nerves and the potential for neural regeneration.

Adult↗
PubMed1993

[Neurofibromin].

Explore the source record for details and available documents.

Genes, Neurofibromatosis 1↗
PubMed1993

Distraction bone healing.

Bone formation by distraction was studied using three different experimental models: (1) Physeal distraction of the sheep radius was performed in 20 animals. (2) Distraction after osteotomy of the radius was carried out in 39 sheep. (3) Mandibular distraction after osteotomy was performed in 17 sheep. Formation of the organic matrix and osteogenesis were studied by radiographic, histologic, and biochemical methods as well as by electron microscopy. The mode of osteogenesis was essentially similar in all of these distraction models. Bone formation was preceded by organization of the collagenous matrix in the distraction area. In the beginning of the distraction, the gap was composed of a heterogeneous cell population, with large polymorphic fibroblast-like cells. The cells in the central part differentiated into fibroblasts, which remained functionally active as long as distraction proceeded. During physeal distraction, bone formed from the epiphyseal and metaphyseal sides as well as from the surrounding perichondrium. Also, in osteotomy distraction of both tubular bone and mandible, bone formed centripetally from the osteotomized bone ends toward the center of the gap. The organic matrix was composed almost solely of Type I collagen in the earliest stages, suggesting that the mode of osteogenesis differs from bone repair by fracture callus. The structure of the distracted segment was mainly lamellar trabecular. Corticalization of the lengthened bone segment occurred gradually after several months.

Animals↗
PubMed1993

Proliferation of the hypertrophic chondrocytes of the growth plate after physeal distraction. An experimental study in rabbits.

Reports on the effects of physeal distraction on chondrocyte proliferation are controversial, and the biologic mechanism of lengthening is still open. Proliferation of the growth plate chondrocytes was studied after gradual physeal distraction in 12 growing rabbits. Distraction of the distal femoral physis was performed with an external fixation device for three to 14 days. Proliferating cells were labeled with 5-bromo-2'-deoxyuridine one hour before killing the animal, and labeled chondrocytes were localized with a specific monoclonal antibody. Labeled chondrocytes were observed in the hypertrophic zone after distraction of three to seven days, in addition to labeling in the proliferative zone; in the remaining physes, the distribution of labeled cells was normal. Physeal widening occurred in all distracted specimens, and a fracture-separation, usually through the hypertrophic zone, in all but one. The labeled hypertrophic cells were seen on the epiphyseal side of the separation gap, five to 20 cells in each specimen. Although hypertrophic chondrocytes are known to be metabolically active, proliferation of these cells has never been reported before. Hypertrophic chondrocytes seem capable of proliferation under special circumstances.

Animals↗