Search PubMed⌕ Search

Biomedical subjects

K P Pritzker

Publications and source records attributed to K P Pritzker.

At least 19 recordsLinked to original sources
PubMed2001

High frequency acoustic parameters of human and bovine articular cartilage following experimentally-induced matrix degradation.

Matrix degradation and proteoglycan loss in articular cartilag eare features of early osteoarthritis. To determine the effect of matrix degradation and proteoglycan loss on ultrasound propagation in cartilage, we used papain and interleukin-1alpha to degrade the matrix proteoglycans of human and bovine cartilage samples, respectively. There is also minor collagen alteration associated with these chemical degradation methods. We compared the speed of sound and frequency dependent attenuation (20-40 MHz) of control and experimental paired samples. We found that a loss of matrix proteoglycans and collagen disruption resulted in a 20-30% increase in the frequency dependent attenuation and a 2% decrease in the speed of sound in both human and bovine cartilage. We conclude that the frequency dependent attenuation and speed of sound in articular cartilage are sensitive to experimental modification of the matrix proteoglycans and collagen. These findings suggest that ultrasound can potentially be used to detect morphologic changes in articular cartilage associated with the progression of osteoarthritis.

Adult↗
PubMed1999

The vascularized pig fibula bone flap model: effects of multiple segmental osteotomies on growth and viability.

Previous work by this laboratory introduced the pig fibula bone flap as a model for the study of the pathophysiology of vascularized bone flaps. Anatomic and hemodynamic studies demonstrated a significant (p < 0.05) decrease in vascular perfusion after a series of segmental osteotomies and rigid fixation (lag screws and miniplates) in the distal end of the flap, suggesting that blood flow to the distal osteotomized segment of the flap may be impaired. Killing the animals after blood flow studies precluded assessment of the effect of these hemodynamic changes on bone healing. Therefore, the aim of this study was to assess the pig fibula bone flap model with respect to viability, healing, and subsequent growth after multiple segmental osteotomies and rigid fixation to contribute to the understanding of vascularized bone flap pathophysiology. Yorkshire pigs (20 to 25 kg) were used for all experiments. Eight pigs underwent unilateral elevation of a vascularized fibula bone flap, which was osteotomized into three segments and orthotopically rigidly fixed using a 2.4-mm mandibular reconstruction plate. The left fibula remained as the control. Fluorochrome labels were injected to assess bone viability and turnover, and both fibulae were assessed for growth radiologically. The fibulae were harvested 21 days postoperatively (when the animals were killed), and bone healing was assessed histologically and clinically. There were no significant differences in preoperative and postoperative lengths of the osteotomized fibulae compared with the controls, suggesting that there was no impairment of growth potential after multiple segmental osteotomies and rigid fixation. Significant (p < 0.05) bony hypertrophy of the osteotomized fibulae was noted when compared with controls. Mobility was observed in 3 of the 32 osteotomies (9 percent), occurring across one proximal and two distal osteotomies in association with failure of fixation. However, histologic and fluorochrome assessment confirmed the viability of all bone segments, as supported by the presence of tetracycline given 2 days postoperatively. The pig fibula bone flap model is well tolerated by the pig. Multiple segmental osteotomies and rigid fixation, previously associated with a significant decrease in blood flow in the distal segment, did not impair either growth potential, viability, or healing ability. It is suggested that the pig fibula is a suitable model for the study of bone flap pathophysiology.

Animals↗
PubMed1998

Allotype immunoglobulin enhances alkaline phosphatase activity: implications for the inflammatory response.

To understand the interactions among components of the immune/inflammation response, we studied the effects of immunoglobulins on the phosphatase activity of alkaline phosphatase in vitro. Bovine intestinal alkaline phosphatase was incubated with substrate in the presence of allotypic and xenotypic immunoglobulin. We found that bovine but not rabbit immunoglobulin enhanced the phosphatase activity of bovine intestinal alkaline phosphatase. Similarly, human but not bovine immunoglobulin G enhanced human placental alkaline phosphatase activity. By enhancing alkaline phosphatase activity, immunoglobulins bound to alkaline phosphatase may assist physiologic transport functions and enhance resolution of the inflammatory response. Further, in clinical conditions with high immunoglobulin concentrations, the serum alkaline phosphatase recorded may have spuriously high values.

Alkaline Phosphatase↗
PubMed1998

neu/erbB-2 amplification identifies a poor-prognosis group of women with node-negative breast cancer. Toronto Breast Cancer Study Group.

PURPOSE: It remains a challenge to predict which women with axillary node-negative (ANN) breast cancer at greatest risk of relapse may benefit most from adjuvant therapy. Increases in neu/erbB-2 have been implicated in breast cancer prognosis. Although overexpression has been investigated extensively, this study represents the first prospective assessment of the prognostic value of neu/erbB-2 DNA amplification in a cohort of women with newly diagnosed ANN. METHODS: A consecutive series of women was monitored for recurrence (median follow-up duration, 36 months) and tumors from 580 individuals were analyzed for amplification. The association of amplification with risk of recurrence was examined in survival analyses with traditional and histologic markers as prognostic factors. RESULTS: Neu/erbB-2 was amplified in 20% of cases. We found an increased risk of disease recurrence when neu/erbB-2 was amplified > or = twofold that persisted with adjustment for other prognostic factors (relative risk, 2.36; P = .002). We found some evidence that amplification was more important in patients who received chemotherapy compared with untreated patients. CONCLUSION: neu/erbB-2 amplification is an independent prognostic factor for risk of recurrence in ANN breast cancer. Women with tumors without neu/erbB-2 amplification have a good prognosis; aggressive therapy in this group is therefore difficult to justify. On the other hand, even with adjuvant chemotherapeutic treatment, women whose tumors exhibit neu/erbB-2 amplification have an increased risk of recurrence. We encourage a randomized trial to compare more aggressive adjuvant chemotherapy versus standard chemotherapy for ANN women whose tumors exhibit neu/erbB-2 amplification.

Axilla↗
PubMed1997

Fresh osteochondral allografts for post-traumatic osteochondral defects of the knee.

We used fresh small-fragment osteochondral allografts to reconstruct post-traumatic osteochondral defects in 126 knees of 123 patients with a mean age of 35 years. At a mean follow-up of 7.5 years (2 to 20), 108 knees were rated as successful (85%) and 18 had failed (15%). The factors related to failure included age over 50 years (p = 0.008), bipolar defects (p < 0.05), malaligned knees with overstressing of the grafts, and workers' compensation cases (p < 0.04). Collapse of the graft by more than 3 mm and of the joint space of more than 50% were seen more frequently in radiographs of failed grafts. Our encouraging clinical results for fresh small-fragment osteochondral allografts show that they are indicated for unipolar post-traumatic osteochondral defects of the knee in young active patients.

Adolescent↗
PubMed1996

Osteoarthritis of the hand in nonhuman primates: a clinical, radiographic, and skeletal survey of Cayo Santiago rhesus macaques.

We describe the relative prevalence and pattern of distribution of osteoarthritis (OA) in the hands of elderly (> 15 years) rhesus macaques using clinical, radiographic, and skeletal examinations. In the clinical study the prevalence of nodes was 72% and 16% in the distal inter-phalangeal joints (DIPJ) and proximal inter-phalangeal joints (PIPJ), respectively, 31% of all monkeys had polyarticular nodes. Radiographic OA was present in 55%, 9.1%, and 0% of the DIPJs, PIPJs, and thumb base, respectively. Skeletal OA as defined by joint surface eburnation for the DIPJ, PIPJ, and thumb base were 16%, 8%, and 2%, respectively. A similar pattern of hand OA with humans is described except for the thumb base OA. This may be due to the relatively rudimentary manipulative role of the macaque thumb. The finding of polyarticular nodal OA raises the possibility of a common pathogenensis for IPJ OA amongst primates.

Animals↗
PubMed1996

Regulation of alkaline phosphatase: implications for calcium pyrophosphate dihydrate crystal dissolution and other alkaline phosphatase functions.

OBJECTIVE: Alkaline phosphatase (ALP), an enzyme with pyrophosphatase (PPiase) activity can dissolve calcium pyrophosphate dihydrate (CPPD) crystals. We studied the effects of enzyme inhibitors such as bisphosphonates, orthovanadate, calcium, cadmium, and ascorbic acid on PPiase activity of ALP as well as on phosphate ester hydrolysis (Pase) activity and compared these effects to those on CPPD crystal dissolution. METHOD: An in vitro model system for crystal enzyme interaction was used to assess CPPD crystal dissolution. RESULTS: Bisphosphonates inhibited ALP Pase activity more than ALP PPiase activity at the same concentrations. Calcium inhibited ALP PPiase activity, but not ALP Pase activity. Orthovanadate and cadmium inhibited ALP PPiase activity more than ALP Pase at the same concentrations. The inhibition rates of ALP PPiase at the same concentrations were orthovanadate > cadmium > calcium. Although ALP Pase activity was not inhibited, at high concentrations, ascorbic acid slightly inhibited ALP PPiase activity. Bisphosphonates at high concentrations inhibited ALP CPPD crystal dissolution. The strong inhibitory effects of bisphosphonates on ALP CPPD crystal dissolution compared to those on ALP PPiase activity suggest that bisphosphonates inhibit crystal dissolution by their affinity for the CPPD crystal surface. Calcium, orthovanadate, and cadmium inhibited ALP CPPD dissolution. The inhibition rates of ALP CPPD dissolution at the same concentrations were cadmium > calcium > orthovanadate. Ascorbic acid at high concentrations enhanced ALP CPPD dissolution. CONCLUSION: These effects of different inhibitors on ALP PPiase and CPPD dissolution suggest that ALP CPPD crystal dissolution depends on binding of ALP CPPD crystals as well as the PPiase activity of the bound ALP. Because of its ubiquitous and broad phosphatase activity including PPiase activity, ALP may have a critical role in cell energy metabolism.

Alkaline Phosphatase↗
PubMed1995

Imaging of immature articular cartilage using ultrasound backscatter microscopy at 50 MHz.

A high frequency sonographic technique-ultrasound backscatter microscopy-was used to visualize the subsurface structure of immature porcine articular cartilage from the knee joint. In 20-week-old pigs, all parts that were scanned, except the weight-bearing regions of the femoral condyles, demonstrated heterogeneous ultrasound backscatter characteristics within the articular cartilage. A trilaminar pattern consisting of hypoechoic, hyperechoic, and anechoic layers ranging from superficial to deep generally was observed, except in the weight-bearing regions of the femoral condyles, where a homogeneous anechoic pattern was seen. In the younger pigs (6 and 10 weeks old), the trilaminar backscatter pattern was not observed. Small, highly echogenic structures that correlated with vascular channels in histologic assessment were observed frequently in the cartilage of younger pigs, but they were seldom present in the cartilage of 20-week-old pigs. Structural details, such as disruption of the subchondral bone and presence of a thickened fibrous layer on the articular surface at the chondrosynovial junction, also were detected with the ultrasound backscatter microscope. We concluded that high frequency ultrasound can be used to visualize the subsurface structure of immature articular cartilage and some of its developmental changes. Further research is required to explain the mechanism underlying the observed backscatter characteristics of immature articular cartilage and to study its potential for the imaging of pathologic changes.

Animals↗
PubMed1995

The effect of pamidronate in a new model of immobilization in the dog.

Bone loss resulting from immobilization or disuse has been shown in humans following paralysis or bedrest. We have developed a new model of immobilization in the dog which is reversible and we have studied the effect of pamidronate (APD) in this model. Twelve mature beagle dogs were fitted with specially designed mesh jackets. These jackets were used to bind the left forelimb against the body of the dog, thereby preventing weight bearing on that limb. The experimental group (n = 6) was treated with an I.V. dose of 0.45 mumol/kg/day APD (pamidronate) for 7 days followed by 3 weeks without treatment. This cycle was repeated 3 times for a total of 12 weeks. The control group (n = 6) followed the same pattern, but received only saline injections. At the end of the experiment, the dogs were sacrificed and the humeri and radii cleaned of soft tissues. Mineralization profiles, which determine the distribution of mineralization densities of the cortical and trabecular bone were obtained and the main fractions were analyzed chemically. Static histomorphometric parameters were determined on 5 microns undecalcified sections from the distal humerus and on 50 microns section of the humeral shaft. Three point bending and torsional testing were performed on the radius. Immobilization induces hypomineralization in cortical and cancellous bone but is prevented by APD treatment in cancellous. Immobilization in this model induces osteopenia and increases turnover in cancellous bone. These effects are counteracted by APD. Finally, cortical bone density and stiffness are reduced by immobilization but this is prevented by APD treatment. This experiment shows that the mature dog model is useful to study the immobilization-induced increase of bone turnover and concomitant decrease in bone density, stiffness and mineralization. It also shows that these effects of immobilization can be prevented by treatment with the bisphosphonate pamidronate.

Animals↗
PubMed1995

Osteoarthritis staging: comparison between magnetic resonance imaging, gross pathology and histopathology in the rhesus macaque.

Although osteoarthritis (OA) is the most common cause of articular skeletal disability in humans, assessing progression (staging) with noninvasive methods remains a major clinical problem. Using the rhesus macaque animal model, the objective of this study was to compare OA staging by noninvasive magnetic resonance imaging (MRI) against gross pathology and histopathology. Right knee joints from 18 rhesus macaques were used in this study. Using a four-point ordinal scale for each of the above-mentioned modalities, the lateral and medial femoral condyle and tibial plateau of each knee joint was independently scored for OA severity, i.e. normal, mild OA, moderate OA and severe OA. Correlation between each staging system was performed using Stuart's Tau-c correlation coefficient. By our criteria, MRI staging correlated as well with gross pathology (tau = 0.75) and histopathology (tau = 0.80) as did gross pathology with histopathology (tau = 0.78). Our study shows that MRI is a promising noninvasive modality to evaluate the severity of OA. MRI appears to be sensitive for demarcating the presence and extent of focal OA cartilage lesions. However, at this time, while MRI is sensitive for detecting OA change it cannot distinguish between certain lesions such as superficial cartilage matrix fibrillation and hypertrophy both of which show elevated signal intensity.

Animals↗
PubMed1995

Calcium pyrophosphate dihydrate (CPPD) crystal dissolution by alkaline phosphatase: interaction of alkaline phosphatase on CPPD crystals.

OBJECTIVE: As alkaline phosphatase (ALP) can dissolve calcium pyrophosphate dihydrate (CPPD) crystals, and as dissolution is facilitated when the enzyme is proximate to the crystals, we studied the mechanism of ALP interaction with CPPD crystals in vitro. METHODS: ALP was incubated with CPPD crystals in an in vitro model system. Fluorescein isothiocyanate conjugated alkaline phosphatase (FITC-ALP), alkaline phosphatase product staining of calcium pyrophosphate dihydrate (CPPD) crystals and scanning electron microscopy were used to visualize ALP-CPPD crystal interactions. RESULTS: ALP preferentially binds to the small end faces (optical 010 faces) of CPPD crystals. Etch pits indicative of dissolution were demonstrated coexistent with ALP crystal binding and ALP pyrophosphohydrolytic activity. CONCLUSION: ALP binding to CPPD crystals is preferential for the smallest end faces (optical 010 faces). As ALP crystal binding is altered by ions but not by heat inactivation of ALP, ALP-CPPD crystal binding is considered a nonenzymatic mechanism distinct from ALP pyrophosphohydrolytic activity. Our study demonstrates that ALP binds and dissolves CPPD crystals in a stereoselective manner. This suggests that the CPPD crystal dissolution rate is limited by the availability of surface area on the crystal faces most susceptible to ALP binding.

Alkaline Phosphatase↗
PubMed1995

Osteoarthritis in rhesus macaque knee joint: quantitative magnetic resonance imaging tissue characterization of articular cartilage.

OBJECTIVE: To assess cartilage matrix quality variation by anatomical location and extent of osteoarthritis (OA) using quantitative magnetic resonance imaging (MRI) and to compare the anatomic MR morphologic features with corresponding histological findings. METHODS: We studied 18 fully encapsulated right knee joints from a population of rhesus monkeys with a high incidence of degenerative arthritis resembling human OA. Relaxation times (T1 and T2) spin density, and cartilage thickness were determined along 8 contiguous anteroposterior segments of articular cartilage. Histological slides, prepared in the same plane as the MR image, were assessed for OA severity. Using a modification of Mankin's OA classification, each quadrant was grouped into normal (0), mild (1), moderate (2), or severe OA (3). Histopathological scores served as the standard and corresponding MR quadrants were classified accordingly. RESULTS: Cumulative results revealed a significant decrease in T1 relaxation time (p = 0.04) and an increase in T2 relaxation time (p = 0.03) in the mild and severe OA groups, respectively. Statistically significant changes in spin density and cartilage thickness measurements were not observed. MR signal intensity abnormalities in selected regions of interest were demarcated and studied histologically. Regions with histological proliferating chondrocytes or fibrillated cartilage showed bright signal intensity on MR images (TR = 3000 ms; TE = 10 ms) and corresponded with elevated T1 and T2 values. Histological regions of collagen condensation showed low signal intensity on MR images (TR = 3000 ms; TE = 10 ms) and corresponded with decreased T1 and T2 relaxation times. CONCLUSION: Topological quantitative MRI relaxation time assessment demonstrates increasing cartilage matrix quality variation with OA progression.

Animals↗
PubMed1995

Polyamines enhance calcium pyrophosphate dihydrate crystal dissolution.

OBJECTIVE: Alkaline phosphatase (ALP), an enzyme with pyrophosphatase (PP(i)ase) activity, can dissolve calcium pyrophosphate dihydrate (CPPD) crystals. We investigated the CPPD crystal dissolution activity of polyamines, substrates known to enhance PP(i)ase activity. METHODS: An in vitro model system for crystal enzyme interaction was used to assess CPPD crystal dissolution both biochemically and morphologically. RESULTS: We demonstrated biochemically and morphologically that polyamines such as spermine and spermidine can enhance CPPD crystal dissolution activity of ALP. Polyamines enhanced ALP induced CPPD crystal dissolution and ALP PP(i)ase activity differentially. By scanning electron microscopy, we observed that polyamines enhanced dissolution stereoselectively at the small end faces (optical 010 faces) of CPPD crystals, indicated by the presence of etch pits. CONCLUSION: Polyamines assist ALP to promote the stereoselective dissolution of CPPD crystals. In addition to implications for CPPD crystal dissolution, as ALP is present intracellularly, these studies suggest that polyamines and ALP have synergistic effects when ALP PP(i)ase activity is required for intracellular energy metabolism.

Alkaline Phosphatase↗
PubMed1994

Arthropathy in thalassaemia patients receiving deferiprone.

The iron chelator deferiprone (L1) reduces tissue iron stores in iron-loaded patients. Three of sixteen patients treated with deferiprone developed joint pain and swelling without evidence of systemic lupus erythematosus (SLE). Articular cartilage, synovial hypertrophy and iron deposition, and synovial lining cell proliferation, with no inflammatory or allergic reaction, were observed on synovial exploration and biopsy. Symptoms resolved partly or completely during continued drug administration. We hypothesise that deferiprone-induced shifts of iron to synovium resulted in tissue damage, accelerated by free-radical formation during incomplete complexation of iron and this bidentate chelator. This deferiprone-associated symptom complex is not associated with drug-induced SLE, and does not progress in severity during continued therapy.

Adolescent↗
PubMed1994

Analysis of collagens solubilized from cartilage of normal and spontaneously osteoarthritic rhesus monkeys.

Osteoarthritis (OA) is a disorder which results in the destruction of the articular cartilage and the remodeling of the subchondral bone in synovial joints. We have analyzed the cartilage collagen from normal and osteoarthritic free-ranging rhesus monkeys from the Cayo Santiago colony. The cartilage samples were assigned a severity score based on histological staging system and were divided into four groups (normals, mild OA, moderate OA and severe OA). After a 4.0 M guanidinium chloride (GuCl) extraction, the remainder of the cartilage was digested with pepsin and the collagen was salt precipitated at 2.5 M and 4.3 M NaCl. The GuCl solubility of the osteoarthritic cartilage increased compared to normals. Collagen extractability by GuCl also increased with the severity of disease. Pepsin digestion followed by salt precipitation shows that collagen from rhesus osteoarthritis cartilage is more easily extracted than from normal cartilage. With an anti-type I collagen antibody we have detected the presence of type I collagen in the severe OA cartilage samples but not in the milder OA groups or in normal cartilage. Total collagen content decreases with severity of OA, which is not due to changes in propyl hydroxylation because examination of collagen hydroxylation, based on hydroxyproline analysis, shows no difference between OA and normal cartilage.

Animals↗
PubMed1994

Vitamin B6 deficiency experimentally-induced bone and joint disorder: microscopic, radiographic and biochemical evidence.

In the present study the effect of pyridoxine deficiency on the ultrastructure and morphology of bone and its metabolism was examined in the rapidly growing chick. Pyridoxine-deficient animals had tibias of reduced dry weight and cortical thickness. Histomorphometry demonstrated a disproportionately high eroded surface, lower amount of osteoid tissue and reduced mineralized trabecular width. Anterior-posterior radiographs of the tibiotarsometatarsal joint showed reduced secondary ossification centres and coarse trabeculation. Decalcified metaphyseal cartilage showed irregular trabeculas and a markedly reduced amount of Fast-green counterstain matrix suggesting that there is less collagen present and in turn less availability for matrix to be laid down for later calcification. Plasma activity of the bone alkaline phosphatase isoenzyme (EC 3.1.3.1) was decreased. Plasma Ca and PO4 levels did not vary. The present bone study referring to a pseudo-lathyritic state in which collagen maturation is not completely achieved supports the hypothesis that pyridoxine is an essential nutrient for the connective tissue matrix.

Alkaline Phosphatase↗
PubMed1994

Calcium pyrophosphate dihydrate crystal deposition and other crystal deposition diseases.

Calcium pyrophosphate dihydrate (CPPD) crystal deposition disease continues to be of intense clinical and basic science interest. Follow-up of studies of hereditary CPPD crystal deposition indicate differences from the common sporadic disease. The results of a prospective study of CPPD crystal deposition arthropathy confirm that clinical symptoms appear to be independent of radiologic progression. Novel clinical presentations include association with pregnancy and simulation of meningitis. CPPD crystal deposition pathology in synovium ultrastructurally resembles that in cartilage. Factors such as the presence of ATP can induce experimental calcifications in tissue culture that resemble CPPD crystal deposition. Interleukin-8 and tyrosine phosphorylation of neutrophil protons can mediate CPPD crystal deposition-associated inflammation. The control of crystal function and dissolution recently has been the subject of many general reviews. The theory outlined in these papers is important for understanding CPPD crystal deposition and basic phosphate crystal formation and dissolution.

Arthritis, Gouty↗