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排序方式: 共有188条查询结果,搜索用时 12 毫秒
11.
Mistry PK Sirrs S Chan A Pritzker MR Duffy TP Grace ME Meeker DP Goldman ME 《Molecular genetics and metabolism》2002,77(1-2):91-98
Type 1 Gaucher's disease (GD) is recognized for striking but unexplained phenotypic diversity. Rarely, severe pulmonary hypertension (PH) may occur in GD but its clinical spectrum, determinants or its response to enzyme replacement therapy (ERT)+/-vasodilators is not known. One hundred and thirty-four consecutive patients with Type 1 GD were screened to estimate right ventricular systolic pressure (RVSP) by Doppler echocardiography. Ninety-four patients were on ERT and 40 were untreated. Eight additional GD patients were studied that represented consecutive tertiary referrals with severe PH. Angiotensin converting enzyme (ACE) gene polymorphisms and acid beta-glucosidase gene (GBA) mutations were determined by DNA analysis. Mild, asymptomatic PH (RVSP>35<50 mmHg) was prevalent in Type 1 GD: 30% in untreated patients and 7.4% among patients receiving ERT (P<0.001). Splenectomy was strongly associated with severe, life-threatening PH: all patients with severe PH (RVSP 50-130 mmHg) were asplenic compared to only 31% of patients with RVSP<50 mmHg (Odds ratio [OR] 28.8, 95% CI 1.6-531.6, P<0.001). Other characteristics of patients presenting with severe PH were poor compliance to ERT (4/9 patients) or no ERT (5/9 patients), a family history of a sib with GD and PH (2/2 patients), an excess of ACE I allele (OR 2.3, 95% CI 1.1-4.9, P=0.034) and an excess of non-N370S GBA mutation (OR 6.0, 95% CI 1.1-33, P=0.003). Severe PH was ameliorated by ERT+/-vasodilators during 4.6+/-4.0 yr (range 1-12 yr) follow-up; three patients were initially considered for lung transplantation but improved such that they are no longer active transplant candidates. Our study reveals a remarkable predisposition for PH in type 1 GD. Progression to severe, life-threatening PH occurs in the presence of additional genetic factors (non-N370S GBA mutation, positive family history, and ACE I gene polymorphism) and epigenetic modifiers (i.e., asplenia and female sex). Splenectomy should be avoided and in high-risk patients, ERT+/-vasodilators/coumadin should be initiated. 相似文献
12.
Zhao YF Mendes M Symington JM Listrom RD Pritzker KP 《The International journal of oral & maxillofacial implants》1999,14(6):889-897
Histologic and histomorphometric results of bone growth around titanium alloy screw-type implants after Surgibone grafting in New Zealand white rabbits are presented. At 21 days, new bone was formed along the surface of the implant. At 84 days, newly formed bone replaced almost all of the trabecular bone of the graft and reached the shoulder level of the implant. There was a higher percentage of host bone area at 84 days than at any of the earlier experimental periods (P < .01). The average mineral apposition rates ranged from 1.82 to 2.35 microns/day in original bone and 2.55 to 2.80 microns/day in newly formed bone. The results suggest that Surgibone grafting in combination with dental implants can be used to increase the height of the recipient bone and therefore aid in the fixation of the implant in this animal model. 相似文献
13.
We described a chick periosteal osteogenesis model at the light microscopic level and biochemically. To confirm that morphologically identifiable bone is being formed, we performed an ultrastructural study of this model. Samples of freshly dissected periostea, as well as whole calvariae, were fixed in glutaraldehyde. Cultured tissues were subsequently harvested and similarly fixed at 2, 4, and 6 days of culture. Examination of freshly dissected periostea showed that these tissues contained many fibroblast-like cells within a loosely arranged connective tissue. There was no evidence of osteoid or mineral in this tissue. Whole calvarial explants contained well-mineralized bone surrounded by an osteoid seam. At 2 days in culture there was an increase in cellular organization as well as extracellular matrix production. No mineral was detected. By 4 days a non-mineralized osteoid matrix was present, which consisted of densely packed, highly oriented, crossbanded collagen fibrils. Early spherical mineral deposits were seen. The osteoid was surrounded by a multilayer of osteoblast-like cells. The 6-day cultures all contained well-mineralized matrix. The mineral was identified by electron diffraction to be apatite. The data suggest that this in vitro model accurately recapitulates the highly ordered and controlled sequence of events leading to de novo bone formation. 相似文献
14.
Age-related changes in the human femoral cortex 总被引:4,自引:0,他引:4
Bone undergoes structural changes with aging, but the nature of qualitative changes remains to be established. Blocks of midshaft femur were taken at autopsy from men of four different age groups: 20-25 years, 40-45 years, 60-65 years, and 80-85 years. Each femoral specimen was analyzed by density fractionation, a technique that allows the separation of bone by extent of mineralization and maturity. In the 20-25 group, lower density bone predominates. The 40-45 group is characterized by more highly mineralized bone with an increase in the 2.1-2.2 g/cc fraction. At 60-65 years, an increase in the lower density fraction was found, indicating an increase in new bone formation. At 80-85 years, there is an increase in the highest density bone (2.2-2.3 g/cc), which may represent regions of interstitial bone not properly removed through remodeling processes. Chemical studies did not reveal any change in Ca, P, Ca + PO4, or Ca/P molar ratio with respect to age. X-ray diffraction studies show no changes in apatite crystal size with respect to age or degree of mineralization. Morphological studies documented increased remodeling activity and endosteal trabecularization in the older age groups, as well as increased intracortical porosity. An increase in the highest density fraction with aging may represent a pool of bone mineral that is less accessible to remodeling, which may be the interstitial bone. 相似文献
15.
OBJECTIVE: Calcium pyrophosphate dihydrate (CPPD) crystal deposition disease, a common arthritis affecting the elderly, is characterized by the deposition of CPPD crystals in articular joints. The mechanism underlying disease expression is unknown, but factors contributing to the pathogenesis may involve changes in enzymatic activities involving pyrophosphate and phosphate metabolism. Tissue nonspecific alkaline phosphatase (TNAP) is one of the major enzymes regulating pyrophosphate concentrations in articular joints. We hypothesized that inhibition of TNAP activity at pH = 7.4 by endogenous molecules can lead to CPPD disease pathogenesis. METHODS: We investigated the inhibitory effects of the amino acid cysteine on TNAP's phosphatase, inorganic pyrophosphatase, and CPPD crystal dissolution activities. Kinetic parameters V(max), K(M), concentration for 50% inhibition (I(50)), inhibitor constant (K(I)), and specific activities calculated from Initial Velocity, Eadie-Hofstee, Simple, Dixon, and Secondary plots were used to assess enzyme inhibition. RESULTS: Cysteine inhibited TNAP's phosphatase activity uncompetitively and its inorganic pyrophosphatase activity mix-competitively. CPPD crystal dissolution activity was also inhibited. I(50) values demonstrated that high cysteine concentration is required to inhibit 50% of enzyme activity. K(I) values suggested that inorganic pyrophosphatase activity is inhibited more than the phosphatase activity. Ca(++) and Mg(++) ion concentrations may regulate this inhibition. CONCLUSION:The control of endogenous inhibitors, such as cysteine, that interfere with TNAP's ability to regulate CPPD crystal formation and dissolution in joints could be a potential therapeutic option for CPPD crystal deposition disease. 相似文献
16.
Gross AE Kim W Las Heras F Backstein D Safir O Pritzker KP 《Clinical orthopaedics and related research》2008,466(8):1863-1870
Fresh osteochondral allograft transplantation has been an effective treatment option with promising long-term clinical outcomes
for focal posttraumatic defects in the knee for young, active individuals. We examined histologic features of 35 fresh osteochondral
allograft specimens retrieved at the time of subsequent graft revision, osteotomy, or TKA. Graft survival time ranged from
1 to 25 years based on their time to reoperation. Histologic features of early graft failures were lack of chondrocyte viability
and loss of matrix cationic staining. Histologic features of late graft failures were fracture through the graft, active and
incomplete remodeling of the graft bone by the host bone, and resorption of the graft tissue by synovial inflammatory activity
at graft edges. Histologic features associated with long-term allograft survival included viable chondrocytes, functional
preservation of matrix, and complete replacement of the graft bone with the host bone. Given chondrocyte viability, long-term
allograft survival depends on graft stability by rigid fixation of host bone to graft bone. With the stable osseous graft
base, the hyaline cartilage portion of the allograft can survive and function for 25 years or more.
Each author certifies that he or she has no commercial associations (eg, consultancies, stock ownership, equity interest,
patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article.
Each author certifies that his or her institution has approved the human protocol for this investigation and that all investigations
were conducted in conformity with ethical principles of research. 相似文献
17.
Phillips MR Shen Q Liu X Pritzker S Streiner D Conner K Yang G 《Journal of affective disorders》2007,98(1-2):73-82
BACKGROUND: The potential insensitivity to depression of translated diagnostic instruments makes it difficult to assess the relationship of depressive symptoms to suicide in non-Western cultures. METHODS: Addition of culturally sensitive probes and other modifications were made to the depression section of the Chinese version of the SCID; the standard SCID probes and the expanded-probes are separately used to assess each symptom of depression, the resultant diagnoses and the overall severity of depression. This modified SCID was included in the psychological autopsy interviews with family members and, separately, close associates of 887 suicides and 721 non-suicidal decedents from 23 regions of mainland China. RESULTS: Compared to the standard interview, the expanded-probe method increased reported prevalence of major depressive episode among suicide decedents from 26.4% (234/887) to 40.2% (357/887) and for other deaths from 1.0% (7/721) to 2.1% (15/701). The additional 131 cases identified using the expanded-probe method had substantial social impairment and a greatly elevated risk of suicide compared to those with no depressive symptoms (OR=37.0, 95% CI=17.6-77.6). Inter-observer reliability for major depressive episode between the two independent interviews was greater for the expanded probe method (ICC=0.77 vs. 0.67, P<0.001). For both interview methods there was a strong dose-response relationship between suicide risk and the number and severity of depressive symptoms. LIMITATIONS: This study uses proxy informants to obtain information about the psychological status of deceased subjects; the value of this expanded-probe method for the diagnosis of depression in non-Western cultures needs to be confirmed with living subjects. CONCLUSIONS: Adding culture-appropriate probes about depressive symptoms to standardized diagnostic instruments identifies many Chinese subjects with unrecognized depression. Dimensional measures of depressive symptoms are more powerful predictors of suicide risk than categorical diagnoses. 相似文献
18.
19.
Posttraumatic cartilage hypertrophy: edema or repair? 总被引:1,自引:0,他引:1
K P Pritzker 《The Journal of rheumatology》1991,18(3):314-315
20.