Biomedical subjects

H T Aro

Publications and source records attributed to H T Aro.

At least 37 records · Page 2Linked to original sources

PubMed1999

Complete genomic structure of the mouse cathepsin K gene (Ctsk) and its localization next to the Arnt gene on mouse chromosome 3.

In preparation for gene manipulative experiments in mice we have isolated genomic clones covering the entire murine cathepsin K gene (Ctsk). Sequence analysis revealed that the gene spans 10.1 kb and contains eight exons and seven introns. The sizes of the coding exons 2-7 as well as the pattern of intron sizes are conserved between the human and mouse cathepsin K genes. Genomic organization of the mouse cathepsin K gene also closely resembles those of cathepsins S and L. More than 26% of the Ctsk sequence consists of different repetitive elements. Detailed sequence analysis of 1.7 kb of Ctsk promoter revealed several putative binding sites for transcription factors and two stretches of 280-320 bp which were > 70% homologous with the human cathepsin K promoter. Analysis of genomic clones extending further upstream of the Ctsk gene identified the 3' end of the gene coding for arylhydrocarbon-receptor nuclear translocator (Arnt). This places Ctsk approximately 4.5 kb downstream of Arnt on mouse chromosome 3 at locus 47.9.

5' Untranslated Regions↗

PubMed1999

Expression profiles of mRNAs for osteoblast and osteoclast proteins as indicators of bone loss in mouse immobilization osteopenia model.

An experimental mouse model for disuse osteopenia was developed using unilateral cast immobilization. Analysis of the distal femurs and proximal tibias by quantitative histomorphometry revealed significant osteopenia within 10-21 days of immobilization. At 3 weeks, bone loss was also demonstrated with peripheral quantitative computed tomography as diminished bone mineral content and as concomitant reduction in the cross-sectional moment of inertia. These structural and geometrical alterations resulted in decreased strength of the distal femurs tested by cantilever bending. Analysis of the underlying cellular and molecular mechanisms of bone loss revealed a rapid increase in bone resorption within 3 days of immobilization. The mRNA levels for cathepsin K, matrix metalloproteinase-9, and tartrate resistant acid phosphatase were all significantly increased during the 21-day immobilization period, but with different expression profiles. These increases were paralleled by an increased number of osteoclasts as measured by histomorphometry. By day 6 of immobilization, the balance of bone turnover was further shifted toward net bone loss as the mRNA levels for major bone components (type I collagen and osteocalcin) were decreased. In histomorphometric analysis this was observed as reduced rates of mineral apposition and bone formation after 10 days of immobilization. The results of this study demonstrate that immobilization has a dual negative effect on bone turnover involving both depressed bone formation and enhanced bone resorption.

Animals↗

PubMed1999

Porous bioactive glass matrix in reconstruction of articular osteochondral defects.

BACKGROUND AND AIMS: This study was carried out to investigate the use of porous bioactive glass implants in promotion of articular cartilage and subchondral bone repair in large osteochondral joint defects. MATERIAL AND METHODS: Two conical osteochondral defects (top diameter 3.0-3.2 mm) were drilled into the patellar grooves of the distal femurs in the rabbit. The defects, extending (approximately 6-7 mm) from the surface of the articular cartilage to the subchondral marrow space, were reconstructed with size-matched porous conical implants made of sintered bioactive glass microspheres (microsphere diameter 250-300 microm, structural implant compression strength 20-25 MPa) using press-fit technique. The implant surface was smoothened to the level of the surrounding articular cartilage. One of the two defects in each femur was left empty to heal naturally and to serve as the control. At 8 weeks, the defect healing was analyzed with use of a semiquantitative histological grading system, histomorphometry of subchondral bone repair, back-scattered electron imaging of scanning electron microscopy (BEI-SEM), and a microindentation test for characterization for the stiffness properties of the cartilage repair tissue. RESULTS: The porous structure of the bioactive glass implants, extending from the articular defect of the patellar groove into the posterior cortex of the femur, was extensively filled by new bone. Cartilage repair varied from near-complete healing by hyaline cartilage to incomplete healing predominantly by fibrocartilage or fibrous tissue. There were, however, no statistical differences in the histological scores of repair between the glass-filled and control defects, although the sum of the averages of each category was lowest for the bioactive glass filled defects. The indentation stiffness values of all the defects were also significantly lower than that of normal cartilage on the patellar groove. CONCLUSIONS: Porous textures made by sintering bioactive glass microspheres may expand the opportunities in reconstruction of deep osteochondral defects of weight-bearing joints. The implants act mechanically as a supporting scaffold and facilitate the penetration of stromal bone marrow cells and their chondrogenic and osteogenic differentiation. Ionic properties of the bioactive glasses make the substances highly potential even as delivery systems for adjunct growth factor therapy.

Animals↗

PubMed1998

Intramedullary fixation of high subtrochanteric femoral fractures: a study comparing two implant designs, the Gamma nail and the intramedullary hip screw.

OBJECTIVE: To compare two implants, the Gamma nail and the intramedullary hip screw (IMHS ), in the treatment of high subtrochanteric femoral fractures. STUDY DESIGN: Prospective, nonrandomized clinical study. METHODS: Eighty-seven consecutive patients with high subtrochanteric fractures of the Russell-Taylor Types 1A and 1B were treated with intramedullary fixation. The first fifty patients were treated with the Gamma nail and the next thirty-seven with the IMHS. The results of these operations were evaluated after a minimum follow-up of twelve months, and special emphasis was put on the complication rate. RESULTS: The number of noninfectious complications (intraoperative fractures, postoperative refractures and fixation failures) was significantly higher (p = 0.037) in the Gamma group (11 of 50, 22 percent) than in the IMHS group (2 of 37, 5 percent). The complication most often associated with the Gamma nail, postoperative fracture of the femoral shaft (six in our Gamma group), was not encountered with the use of the IMHS. The Gamma group also included three cases of intraoperative trochanteric extension of the fracture versus none in the IMHS group. The IMHS group included two mechanical fixation failures. CONCLUSIONS: The lower complication rate associated with the use of the IMHS implant could be attributable in part to the learning curve in the use of intramedullary implants. However, we consider that the evolution of the implant design contributes to the result.

Adolescent↗

PubMed1998

Incorporation of cortical bone allografts and autografts in rats: expression patterns of mRNAs for the TGF-betas.

Healing of bone grafts is dependent on the rate of new bone formation. To understand better the regulation of new bone formation in the graft we have studied local production of TGF-beta1, 2 and 3, and of the small proteoglycans by determining their mRNA levels in a rat bone graft model. These mRNA levels were compared to the healing rates of autografts and allografts, as determined by histology, UV-microscopic evaluation of tetracycline-labeled new bone formation, microradiography and mechanical testing at 1, 2, 4 and 8 weeks of healing. Analyses showed that, analogous to slower bone formation in allografts, the induction of TGF-beta1 gene expression was slower than in allografts, when compared with autografts. A similar delay was seen in decorin gene expression. The results agree with the suggested role of TGF-beta1 in induction of type I collagen and osteonectin production. Our findings thus support the view that locally produced TGF-beta1 plays a role in normal graft incorporation, while local production of TGF-beta3, and particularly TGF-beta2, may be less important in this respect.

Animals↗

PubMed1998

Bone bank service in Finland. Experience of bacteriologic, serologic and clinical results of the Turku Bone Bank 1972-1995.

560 bones were harvested by The Turku Bone Bank between 1972-1995. It was started with massive allografts for bone tumor surgery, but today most are femoral heads for hip revision surgery. The increase in harvested bones nearly trebled from 1984-1989 to 1990-1995. Only 1 positive hepatitis C test was found. There were no hepatitis B or HIV positive donors. The incidence of discarding after screening was 24%, with positive bacterial growth (8%, usually Staphylococcus epidermidis) as the commonest reason. 2 massive grafts with negative cultures when harvesting were positive after thawing and resulted in deep infection. 369 allografts were transplanted. The infection rate of massive allografts for bone tumor surgery was 5/63 in 1973-1995, and 2/52 in 1985-1995. The infection rate for hip revision surgery was 3.4%. The clinical functional results correspond to those reported in larger international series.

Adolescent↗

PubMed1997

Histomorphometric and molecular biologic comparison of bioactive glass granules and autogenous bone grafts in augmentation of bone defect healing.

The applicability of bioactive glass (BG) granules as a substitute for bone grafts was tested by comparing the histologic, histomorphometric, and molecular biologic healing patterns to those of bone autografts and ungrafted bone defects in a rat model. The cellular response in defects filled with BG granules was characterized by continuous overexpression of type III collagen. Osteogenic mesenchymal cells, prior to their differentiation to osteoblasts, organized as a dense periosteumlike layer on the surface of the BG granules. By day 14 new bone formation was more extensive in autografted defects than in BG filled defects (p = 0.039). No cartilage-specific type II collagen mRNA was detectable, confirming the uniformity of intramembranous bone formation. The difference in the initiation of new bone formation was further confirmed by the mRNA analyses of the de novo production of TGF-beta 1 and type I collagen. Autografted defects demonstrated the highest levels of TGF-beta 1 and type I collagen mRNAs during the first 2 weeks of healing, whereas BG-filled defects showed biphasic expression patterns of the same genes. Spontaneous new bone formation in ungrafted bone defects was also characterized by biphasic expression of type I collagen gene. Osteonectin mRNA declined gradually over time in autografted and BG filled defects, whereas unfilled defects showed a gradual increase of osteonectin mRNA during healing. By 8 weeks, about 70% of the BG surface showed evidence of direct new bone contact. Energy-dispersing X-ray analyses confirmed the presence of silica-rich and CaP-rich zones at the bonding interface. In conclusion, the osteoconductive surface of bioactive glass granules efficiently bonds to ongrowing new bone but the material does not reach the capacity of autogenous bone graft in promotion of osteogenesis.

Animals↗

PubMed1997

Different healing rates of bone autografts, syngeneic grafts, and allografts in an experimental rat model.

Matching of donors and recipients for tissue antigens is vitally important for successful transplantation of essentially all organs and tissues, the major exception being bone. The importance of tissue-typing for the healing of bone allografts remains, however, a controversial issue as development of both humoral and cell-mediated immunity against the grafted bone has been observed in some experimental systems. In the present study, we compared the healing patterns of frozen antigen-mismatched allografts, frozen antigen-matched allografts (syngeneic grafts), and fresh cortical bone autografts in an experimental rat model. Histomorphometry of the graft-host interface revealed that new bone formation started significantly earlier in autografts than in allografts or syngeneic grafts. By 2 weeks, the level of new bone formation in the syngeneic grafts had reached that in autografts. Antigen-mismatched allografts, however, continued to exhibit a retarded formation of new bone throughout the union process. These histomorphometric observations were confirmed by molecular biologic analyses for the mRNA levels of type I collagen, which increased earlier and reached a higher level in autografts than in allografts. Use of syngeneic grafts resulted in a longer persistence of type I collagen mRNA expression in the healing tissue than in antigen-mismatched allografts. No apparent differences were seen between allografts and autografts in the expression of type III collagen. No cartilage-specific type II collagen mRNA was observed, indicating that antigen-mismatching or preservation by freezing did not alter the basic mechanism of the interface healing process, although it did slow down the beginning of the process. The experiments suggest that a major antigen mismatch between donor and recipient affects the temporal gene expression of extracellular bone matrix and delays new bone formation at the graft-host interface of cortical bone allografts.

Animals↗

PubMed1997

Spondylodesis in the treatment of segmental instability of the lumbar spine with special reference to clinically verified instability.

We analysed the outcome of 42 consecutive patients suffering from low back pain and segmental instability of the lumbar spine who underwent spondylodesis with transpedicular fixation. There were 29 (69%) females and 13 (31%) males with a mean age of 47 +/- 9 years (range 23 to 66 years). The presence of clinically verified instability was a basic requirement for operative treatment, with at least one clinical sign of instability positive in all patients. Radiological signs of instability were detected in only 74% of the patients. After a postoperative follow-up of one year, lumbar fusion was found in 38 (90%) patients. The fusion was classified as complete in 18 (43%) and as partial in 20 (47%) patients. No fusion there was detected in 4 (10%) patients. Low back pain was completely abolished in 19 (45%) and markedly diminished in 15 (36%) patients in (17%) patients, low back pain had remained unchanged and become worse in 1 (2%) patient. Clinical signs and symptoms of instability were still detected in 10 (24%) patients. As compared to the pre-operative situation, the decrease in clinical instability was statistically significant (p = 0.02). Moreover, a significant correlation was observed between the persistence of clinically verified instability and a poor postoperative outcome in daily activities. Of all patients, 17 (40%) returned to work during the period of follow up. Based on the good outcome of our patients, the results of this study show that clinical signs and symptoms of instability can be successfully used as selection criteria for lumbar spondylodesis.

Adult↗

PubMed1997

Stress fracture of the ulnar diaphysis in a recreational golfer.

PURPOSE: To report a very rare presentation of a stress fracture in a golfer: a stress fracture of the ulnar diaphysis. CASE SUMMARY: A 44-year-old woman had a 4-week history of a sore left wrist. She had been playing golf daily and had had no sudden trauma. Extensor tendinitis was suspected. Symptomatic treatment was given. Radiographs showed a spiculated periosteal reaction of the distal ulnar diaphysis with no signs of fracture or bone destruction. The suggestion of a malignant lesion was raised. Magnetic resonance imaging showed a healing ulnar fracture and edema of the interosseous membrane. DISCUSSION: In golfers, stress fractures may be seen in ribs laterally and in tibias. We believe supination together with overuse of the hand flexor muscles caused the stress fracture presented, which has not previously been reported in golfers. RELEVANCE: Physicians should be aware of the potential for ulnar stress fracture in golfers with wrist pain.

Adult↗

PubMed1996

Mouse cathepsin K: cDNA cloning and predominant expression of the gene in osteoclasts, and in some hypertrophying chondrocytes during mouse development.

We have constructed cDNA clones covering the entire coding region of mouse, human and rabbit preprocathepsin K mRNA for studies on bone turnover. The clone pMCatK-1 for mouse cathepsin K shares 87% nucleotide homology with the corresponding human and rabbit sequences. Analysis of a panel of mouse tissues for tissue distribution of cathepsin K mRNA revealed the highest levels in musculoskeletal tissues: bone, cartilage and skeletal muscle. In situ hybridization of developing mouse embryos was performed to identify the cellular source of cathepsin K mRNA. The strongest mRNA signal was detected in osteoclasts of bone, identified in serial sections by positive TRAP staining. Cathepsin K mRNA was also observed in some hypertrophic chondrocytes of growth cartilages. Association of cathepsin K production with degradation of bone and cartilage matrix suggests that this enzyme and its mRNA levels could serve as markers for matrix degradation in diseases affecting these tissues.

Aging↗

PubMed1995

Expression of type VI, IX and XI collagen genes and alternative splicing of type II collagen transcripts in fracture callus tissue in mice.

The levels of six mRNAs coding for constituent alpha-chains of three minor collagens of cartilage were analyzed in an experimental fracture model in normal and transgenic Del1 mice harboring a deletion mutation of exon 7 in the type II collagen gene. Reduced and retarded chondrogenesis in Del1 mice was evident in callus samples as reduced mRNA levels for the cartilage specific type IX and XI collagens at days 7 and 9 of fracture healing. Analysis of the calluses for alternative splicing of pro alpha 1(II) collagen mRNA also suggested retarded chondrogenesis in Del1 calluses. Another developmentally regulated step in limb development, a switch between alternative promoters of the alpha 1(IX) collagen gene, was also seen during fracture healing but was less obvious in Del1 calluses. Finally, the current data suggest that the abnormality in bone remodelling in Del1 mice involves activation of the genes coding for alpha 1(XI) and alpha 2(VI) collagens.

Alternative Splicing↗

PubMed1995

Synovial fluid culture and blood culture in acute arthritis. A multi-case report of 90 patients.

The use of blood culture methods for culture of synovial fluid (SF) has been suggested to increase the yield of microbes from SF of patients with septic arthritis. We report on a study of 94 SF cultures of 90 adult patients with acute effusions of the knee joint. Three different culture methods were used: conventional agar plate culture, culture with lysis and centrifugation (Isolator) and broth enrichment (BACTEC 6A and 7A). Blood was cultured simultaneously from 76 patients. In the patients with clinical septic arthritis, the SF cultures were positive by all the methods in 8 patients and negative by all the methods in 19 patients. The contamination rate of the SF cultures was 3/215 in the patients without clinical septic arthritis. We conclude that reliable evidence of septic arthritis is emerged from a SF culture by a single method, and that the choice of culture method is less critical. In addition, we discuss the role of blood cultures in the diagnosis of acute arthritides.

Acute Disease↗

PubMed1995

Synovial fluid L-lactic acid in acute arthritis of the adult knee joint.

Determination of synovial fluid (SF) lactic acid has been suggested to be an unspecific indicator of SF leukocytosis, and it is not recommended for differential diagnosis of bacterial arthritis. We analyzed the L-lactic acid content by enzymatic UV-method in 65 SF samples obtained from adult patients with acute knee arthritides. The concentration of L-lactic acid was not high in any SFs with intensive leukocytosis. The mean concentration of L-lactic acid was 13.5 mmol/l (95% confidence intervals 9.4; 17.6 mmol/l) in the synovial-fluid samples from culture-positive arthritis and 5.5 mmol/l (4.9; 6.2 mmol/l) in the synovial-fluid samples from culture-negative arthritis. Determination of SF L-lactic acid is an important part of the diagnostic setup for acute arthritis. Values > 9 mmol/l strongly support occurrence of bacterial arthritis and indicates an immediate onset of the treatment.

Acute Disease↗

PubMed1995

Expression of matrix genes during incorporation of cancellous bone allografts and autografts.

The healing process of cylindrical metaphyseal bone defects filled with fresh autogeneic or frozen allogeneic cancellous bone grafts was studied using histology, biomechanical testing, and molecular biology. The results were compared with the healing pattern observed in nongrafted defects, where a strong initial expression of Type III collagen was followed by slowly starting expression of osteonectin and Type 1 collagen genes. Autogeneic or allogeneic cancellous bone grafts considerably increased the healing rate of the defects. The sequence of healing was similar with both types of grafts, but the maximal levels of Type III and Type I collagen messenger ribonucleic acids (mRNAs) were delayed by 1 week when allografts were used. Histologically, during the initial phase the grafts had an invasion of progenitor mesenchymal tissue within 2 weeks followed by intramembranous bone formation and by a gradual decline in Type I collagen expression. Osteonectin mRNA was present throughout the healing process, but no expression of Type II collagen was seen. Indentation testing showed no significant biomechanical differences between the autografts and allografts. Histology and molecular biology testing results revealed that the production of extracellular matrix starts slower in allogeneic cancellous bone grafts than in autografts, suggesting a basic difference in the initial host tissue response between autogeneic and allogeneic bone grafts.

Animals↗

PubMed1994

Retarded chondrogenesis in transgenic mice with a type II collagen defect results in fracture healing abnormalities.

We have examined the biological and biomechanical consequences of defective type II collagen production for fracture repair employing a genetically engineered mouse line Del1 which was generated by microinjection of a 39-kb mouse pro alpha 1(II) collagen gene construct containing a deletion of exon 7 and intron 7 (Metsäranta et al. [1992] J. Cell Biol. 118:203-212). Standardized tibial fractures were produced in transgenic Del1 mice and their nontransgenic littermates were used as controls. The fracture callus tissues were analyzed at days 7, 9, 14, 28, and 42 using radiography, histomorphometry, biomechanical testing, and Northern analysis of mRNAs for several tissue-specific matrix components. Deficient production of cartilage in Del1 mice resulted in reduced radiographic callus size, smaller cross-sectional area, and impaired biomechanical properties when compared with fractures of nontransgenic control mice. The differences were most evident in 14-day fracture calluses. Consequently mRNAs for cartilage-specific type IX and X collagens and aggrecan were also reduced in Del1 calluses. Levels of type II collagen mRNAs were unaffected since the mutated transgene produced additional type II collagen mRNA molecules. Further abnormalities in the fracture repair process of Del1 mice were observed in callus remodeling. In the control animals a typical feature of external callus remodeling was reduction of callus size during endochondral ossification between days 14 and 28. Such reduction was not observed in the transgenic mice. Histological examination of fracture calluses suggested also a reduction in trabecular surface area, which was found to be even more pronounced in metaphyseal bone of Del1 mice. Despite these differences the biomechanical properties of the calluses in the two groups became similar by day 28 of fracture healing. The results thus suggest that reduced chondrogenesis due to the presence of mutated transgenes in Del1 mice not only causes a temporary impairment in biomechanical properties of healing fractures but also affects later stages of callus remodeling.

Animals↗

PubMed1994

Group II phospholipase A2 in synovial fluid and serum in acute arthritis.

Increased catalytic activity of synovial-type (group II) phospholipase A2 (syn-PLA2), has been associated with cartilage erosions in rheumatoid arthritis and osteoarthritis. The catalytic activity of phospholipase A2 and the concentration of syn-PLA2 were measured in a prospective study in synovial fluid (SF) samples from 66 patients with acute knee joint effusion. The median (range) of the concentration of syn-PLA2 in SF was 210 micrograms/l (80-1480 micrograms/l) in culture-positive septic arthritis, 460 micrograms/l (270-1040 micrograms/l) in reactive arthritis, 780 micrograms/l (120-2710 micrograms/l) in osteoarthritis and 230 micrograms/l (80-1400 micrograms/l) in traumatic joint effusions. High concentrations of syn-PLA2 are found also in SF of patients with arthritides not expected to lead to permanent destruction of cartilage.

Acute Disease↗

PubMed1994

Synovial-fluid D-lactic acid in bacterial and other acute joint effusions.

The use of D-lactic acid in differential diagnosis of bacterial arthritis was evaluated in a prospective study. The concentration of D-lactic acid was determined by the enzymatic UV-method in sixty-eight synovial fluids (SF) and in twenty four sera from adult patients with acute knee effusion. High concentrations of D-lactic acid (> 0.15 mmol/l) were measured most frequently in SF from bacterial arthritis, but also in individual culture-negative SF samples from patients with inflammatory culture-negative joint effusions with and without identified history of infections. Determination of SF D-lactic acid is not useful in differential diagnosis of bacterial arthritis.

Arthritis, Infectious↗