Biomedical subjects

Juha Partanen

Publications and source records attributed to Juha Partanen.

8 recordsLinked to original sources

PubMed2003

FGFR1 is independently required in both developing mid- and hindbrain for sustained response to isthmic signals.

Fibroblast growth factors (FGFs) are signaling molecules of the isthmic organizer, which regulates development of the midbrain and cerebellum. Tissue-specific inactivation of one of the FGF receptor (FGFR) genes, Fgfr1, in the midbrain and rhombomere 1 of the hindbrain of mouse embryos results in deletion of the inferior colliculi in the posterior midbrain and vermis of the cerebellum. Analyses of both midbrain-hindbrain and midbrain-specific Fgfr1 mutants suggest that after establishment of the isthmic organizer, FGFR1 is needed for continued response to the isthmic signals, and that it has direct functions on both sides of the organizer. In addition, FGFR1 appears to modify cell adhesion properties critical for maintaining a coherent organizing center. This may be achieved by regulating expression of specific cell-adhesion molecules at the midbrain-hindbrain border.

Animals↗

PubMed2003

Fgfr1 regulates patterning of the pharyngeal region.

Development of the pharyngeal region depends on the interaction and integration of different cell populations, including surface ectoderm, foregut endoderm, paraxial mesoderm, and neural crest. Mice homozygous for a hypomorphic allele of Fgfr1 have craniofacial defects, some of which appeared to result from a failure in the early development of the second branchial arch. A stream of neural crest cells was found to originate from the rhombomere 4 region and migrate toward the second branchial arch in the mutants. Neural crest cells mostly failed to enter the second arch, however, but accumulated in a region proximal to it. Both rescue of the hypomorphic Fgfr1 allele and inactivation of a conditional Fgfr1 allele specifically in neural crest cells indicated that Fgfr1 regulates the entry of neural crest cells into the second branchial arch non-cell-autonomously. Gene expression in the pharyngeal ectoderm overlying the developing second branchial arch was affected in the hypomorphic Fgfr1 mutants at a stage prior to neural crest entry. Our results indicate that Fgfr1 patterns the pharyngeal region to create a permissive environment for neural crest cell migration.

Alleles↗

PubMed2003

FGF signaling through FGFR1 is required for olfactory bulb morphogenesis.

During development, the embryonic telencephalon is patterned into different areas that give rise to distinct adult brain structures. Several secreted signaling molecules are expressed at putative signaling centers in the early telencephalon. In particular, Fgf8 is expressed at the anterior end of the telencephalon and is hypothesized to pattern it along the anteroposterior (AP) axis. Using a CRE/loxP genetic approach to disrupt genes in the telencephalon, we address the role of FGF signaling directly in vivo by abolishing expression of the FGF receptor Fgfr1. In the Fgfr1-deficient telencephalon, AP patterning is largely normal. However, morphological defects are observed at the anterior end of the telencephalon. Most notably, the olfactory bulbs do not form normally. Examination of the proliferation state of anterior telencephalic cells supports a model for olfactory bulb formation in which an FGF-dependent decrease in proliferation is required for initial bulb evagination. Together the results demonstrate an essential role for Fgfr1 in patterning and morphogenesis of the telencephalon.

Animals↗

PubMed2002

FGFR1 is required for the development of the auditory sensory epithelium.

The mammalian auditory sensory epithelium, the organ of Corti, comprises the hair cells and supporting cells that are pivotal for hearing function. The origin and development of their precursors are poorly understood. Here we show that loss-of-function mutations in mouse fibroblast growth factor receptor 1 (Fgfr1) cause a dose-dependent disruption of the organ of Corti. Full inactivation of Fgfr1 in the inner ear epithelium by Foxg1-Cre-mediated deletion leads to an 85% reduction in the number of auditory hair cells. The primary cause appears to be reduced precursor cell proliferation in the early cochlear duct. Thus, during development, FGFR1 is required for the generation of the precursor pool, which gives rise to the auditory sensory epithelium. Our data also suggest that FGFR1 might have a distinct later role in intercellular signaling within the differentiating auditory sensory epithelium.

Animals↗

PubMed2002

Characteristics of lifetime factors, bone metabolism, and bone mineral density in patients with hip fracture.

Seventy-four postmenopausal women with nonpathological hip fracture were recruited to a study in which they were compared for lifetime factors, some biochemical measurements of bone metabolism, and bone mineral density (BMD), with 40 age-adjusted controls without fracture. The fracture patients were less independent; their walking ability was weaker; their vision was poorer; they had more general diseases (strokes, diabetes, malignant diseases, heart and vascular diseases); more of them had had deliveries; and they were using significantly more loop diuretics, and antidepressant, neuroleptic, and diabetes drugs than the controls. Thirty-seven patients and 19 controls were excluded from the statistical comparison of BMD and the biochemical measurements of bone metabolism because they had had treatments with calcium, vitamin D, bisphosphonates, estrogens, calcitonin, or corticosteroids, and one fracture patient was excluded for primary hyperparathyroidism. The BMD of the upper femur was significantly lower in the fracture group compared with the control group. Serum total calcium (S-Ca) and serum vitamin D (S-25-(OH)-D) were significantly lower and the levels of calcitonin (S-CT) significantly higher in the fracture group than in the control group, but none of the bone formation markers showed significant differences between the study groups. A comparison of patients with cervical and trochanteric fractures showed BMD to be significantly lower in the upper femur in the trochanteric fracture group. There were no significant differences in the biochemical measurements (with the exception that S-CT was higher in the cervical fracture group), nor in the lifetime factors between the fracture types. In conclusion, some lifetime factors and low S-Ca, low S-25-(OH)-D, high S-CT, and low BMD of the upper femur seem to be related to the risk of hip fracture, and low BMD and low S-CT seem to be related to the trochanteric fracture type in postmenopausal women.

Aged↗

PubMed2002

The three mouse actin-depolymerizing factor/cofilins evolved to fulfill cell-type-specific requirements for actin dynamics.

Actin-depolymerizing factor (ADF)/cofilins are essential regulators of actin filament turnover. Several ADF/cofilin isoforms are found in multicellular organisms, but their biological differences have remained unclear. Herein, we show that three ADF/cofilins exist in mouse and most likely in all other mammalian species. Northern blot and in situ hybridization analyses demonstrate that cofilin-1 is expressed in most cell types of embryos and adult mice. Cofilin-2 is expressed in muscle cells and ADF is restricted to epithelia and endothelia. Although the three mouse ADF/cofilins do not show actin isoform specificity, they all depolymerize platelet actin filaments more efficiently than muscle actin. Furthermore, these ADF/cofilins are biochemically different. The epithelial-specific ADF is the most efficient in turning over actin filaments and promotes a stronger pH-dependent actin filament disassembly than the two other isoforms. The muscle-specific cofilin-2 has a weaker actin filament depolymerization activity and displays a 5-10-fold higher affinity for ATP-actin monomers than cofilin-1 and ADF. In steady-state assays, cofilin-2 also promotes filament assembly rather than disassembly. Taken together, these data suggest that the three biochemically distinct mammalian ADF/cofilin isoforms evolved to fulfill specific requirements for actin filament dynamics in different cell types.

Actin Depolymerizing Factors↗

PubMed2002

Functional outcome after displaced femoral neck fractures treated with osteosynthesis or hemiarthroplasty: a matched-pair study of 714 patients.

Osteosynthesis (OS) and hemiarthroplasty (HA) are the commonest treatments for displaced cervical hip fractures in the elderly, but there is no consensus as to which is better. In this prospective matched-pair study we compared these methods as regards functional outcome. In 1989-1996, using the same standardized forms, all displaced cervical hip fractures were prospectively registered in the university hospitals of Oulu in Finland and Lund in Sweden. Osteosynthesis was performed in Lund and hemiarthroplasty in Oulu. Cross-matching, done for age, sex, preoperative residence, and ambulatory ability, resulted in 357 pairs of displaced fractures. More OS than HA patients could manage in their own homes or live semi-independently at 4 months after the fracture. OS patients had better ambulatory ability (p = 0.001) and used walking aids less than HA ones (p = 0.001). The reoperation rates at 4 months were the same among HA and OS patients, but at 1 year, OS patients had a higher reoperation rate (17%) than HA ones (9.5%).

Aged↗

PubMed2001

Hemiarthroplasty or osteosynthesis in cervical hip fractures: matched-pair analysis in 892 patients.

Our aim was to compare hemiarthroplasty (HA) and osteosynthesis (OS) in the treatment of cervical hip fractures using matched-pair analysis, especially with regard to different age groups. Data concerning all hip fractures (excluding pathological fractures) at the University Hospitals of Lund in Sweden, where osteosynthesis with LIH hook-pins was used exclusively, and of Oulu in Finland, using mainly cementless Austin-Moore hemiarthroplasty, were registered during 1989-1996 using the same standardized hip fracture forms filled in preoperatively and at 4 months follow-up. Altogether 446 pairs matched for age, sex, place of residence and walking ability at the time of fracture were found. Patients aged 55-80 years seemed to benefit more, with regard to function, from OS than older patients. At 4 months follow-up, 38% of HA and 48% of OS patients lived in their own homes, 16% and 27% were able to walk alone outdoors, and 11% versus 16% were able to walk without any aids, respectively. At 1 year follow-up, mortality was significantly lower among the OS patients, but the reoperation rate was significantly higher. In conclusion, OS is associated with a better function and lower mortality than HA, especially in younger patients, and it is recommended as the primary treatment for cervical hip fractures in patients younger than 80 years and with good ambulatory capacity, whereas the oldest patients can also be safely treated by HA.

Aged↗